Hormones Section

Hormones

The endocrine system (hormones) has different glands that release various hormones. This system, similar to the nervous system helps one part of the body (the gland) to communicate with another part of the body (the target cell) to perform different functions.. The endocrine glands are important for reproduction, metabolism, growth and other functions.

This system uses hormones to control and coordinate the body’s homeostasis and regulate reproduction, energy level, growth and development, and respond to various environmental stimuli. Hormones and their role in the workings of the endocrine system are as below:

Hormones & Their role in the workings of the endocrine system are as below:

Corticosteroid

Hormone function: Life saving hormone; functions as anti-inflammatory; regulates blood pressure , blood glucose levels  and muscle strength apart from supporting  salt and water balance

Aldosterone

Regulates water balance, salt, and BP

Epinephrine

Causes rapid  heart rate, promotes oxygen intake and blood flow

Norepinephrine

Maintains blood pressure along with other hormones

Growth hormone releasing hormone (GHRH)

Hormone Function:Maintains homeostasis by regulating growth hormone release in the pituitary gland

Thyrotropin Releasing Hormone (TRH)

Hormone Function: Maintains homeostasis by regulating thyroid stimulating hormone release in the pituitary gland

Gonadotropin Releasing Hormone (GnRH)

Hormone Function: Maintains homeostasis by regulating LH/FSH production in the pituitary gland

Corticotropin Releasing Hormone (CRH)

Hormone Function: Maintains homeostasis by regulating adrenocorticotropin release in the pituitary gland

Antidiuretic Hormone (ADH) (vasopressin)

Hormone Function: Supports water retention  from kidneys and controls blood pressure

Adrenocorticotropic Hormone (ACTH)

Hormone Function: It regulates levels of the steroid hormone cortisol, which isreleased from the adrenal glands.

Growth Hormone (GH)

Hormone Function: Regulates growth and development; also stimulates protein production and influences fat distribution

Norepinephrine

Hormone Function: Controls production of sex hormones, estrogen in women and testosterone in men  and supports the production of eggs and sperms.

Oxytocin

Hormone Function: Stimulates contraction of uterus and milk ducts in the breast during pregnancy and labour.

Prolactin

Hormone Function: Initiates and maintains milk production in mothers; impacts sex hormone levels and interferes with periods.

Thyroid-Stimulating Hormone (TSH)

Hormone Function: Stimulates the secretion of thyroid hormones from the thyroid gland

Renin and Angiotensin

Hormone function: Controls blood pressure directly and by regulating aldosterone production from the adrenal glands

Erythropoietin

Hormone Function: Red blood cell (RBC) production

Glucagon

Hormone Function:Raises blood sugar levels and regulates glucose homeostasis

Insulin

Hormone Function:Anabolic hormone, Lowers blood glucose; promotes metabolism of glucose, protein, and fat

Estrogen

Hormone Function:Promotes  female sexual characteristics and reproductive development, influences functioning of uterus and  growth of breasts and protects bone health

Progesterone

Hormone Function:Helps proliferate endothelium (inner lining of the uterus), facilitates  fertilization; supports milk production

Parathyroid Hormone (PTH)

Hormones Function: Important regulator of blood calcium levels along with Vitamin D

Thyroid Hormone

Hormone Function: Controls metabolism; also affects growth, maturation, nervous system activity, and metabolism

Humoral Factors

Hormone Function: Helps develop the lymphoid system

Testosterone

Hormone Function: Develop and maintain male sexual characteristics and promotes libido.

Melatonin

Hormone Function: Releases melatonin during night and facilitates sleep

Know More About Hormones

  • What is adrenaline?
    • Adrenaline is a hormone for a ‘fight or flight’ response during stress.
    • Adrenaline and noradrenline are two similar hormones which are produced in the medulla of the adrenal glands..
    • Adrenaline increases the heart rate, blood pressure, bronchodilates lungs or pupil dilatation,
    • Noradrenaline, is released mainly from the nerve endings of the sympathetic nervous system and small amounts from  adrenal medulla.
    • Noradrenaline is released in low levels into the circulation continuously, but adrenaline release  is during  acute stress.
    • Adrenaline is released within couple of minutes of the stressful event
    • Stress also causes release of cortisol from adrenal cortex which has longer effect than adrenaline and released during longer stresses.

    What happens if I have too much adrenaline?

    • Symptoms of adrenaline release are rapid heartbeat, high blood pressure, anxiety, weight loss, excessive sweating and palpitations
    • Overproduction of adrenaline/noradrenaline may be caused by an adrenal tumour called pheochromocytoma or a paraganglioma (if it is located outside the adrenal but along the nerves of sympathetic nervous system that run through the chest and abdomen).

     

    What happens if I have too little adrenaline?

    • Adrenal deficiency  does not routinely show  as a medical disorder
  • Adrenocorticotropic hormone (ACTH) is made in the pituitary gland. It is needed for your adrenal glands to work properly and help your body react to stress. ACTH stimulates the release of another hormone called cortisol from the cortex (outer part) of the adrenal gland.What is adrenocorticotropic hormone?Corticotrophin-releasing hormone from the hypothalamus acts on the pituitary (inset), which secretes ACTH. ACTH travels to the adrenal glands via the bloodstream (arrow). Cortisol from the adrenal then feeds back to the hypothalamus to shut down the cycle.ACTH is made in the corticotroph cells of the anterior pituitary gland, where it is released in bursts into the bloodstream and transported around the body. Like cortisol, levels of adrenocorticotropic hormone are generally high in the morning when we wake up and fall throughout the day (reaching their lowest level during sleep). This is called a diurnal (circadian) rhythm. Once adrenocorticotropic hormone reaches the adrenal glands, it binds on to receptors causing the adrenal glands to secrete more cortisol, resulting in higher levels of cortisol in the blood. It also increases production of the chemical compounds that trigger an increase in other hormones such as adrenaline and noradrenaline.How is adrenocorticotropic hormone controlled?Secretion of ACTH is controlled by three regions of the body, the hypothalamus, the pituitary gland and the adrenal glands. This is called the hypothalamic–pituitary–adrenal (HPA) axis. When adrenocorticotropic hormone levels in the blood are low, a group of cells in the hypothalamus release a hormone called corticotrophin-releasing hormone which stimulates the pituitary gland to secrete ACTH into the bloodstream. High levels of ACTH are detected by the adrenal gland receptors which stimulate the secretion of cortisol, causing blood levels of cortisol to rise. As the cortisol levels rise, they start to slow down the release of corticotrophin-releasing hormone from the hypothalamus and ACTH from the pituitary gland. As a result, the ACTH levels start to fall. This is called a negative feedback loop.Stress, both physical and psychological, also stimulates ACTH production and hence increases cortisol levels.What happens if I have too much adrenocorticotropic hormone?The effects of too much ACTH are mainly due to the increase in cortisol levels. Higher than normal levels of adrenocorticotropic hormone may be due to:

    Cushing’s disease – this is the most common cause of increased ACTH. It is caused by a non-cancerous tumour called an adenoma located in the pituitary gland, which produces excess amounts of ACTH. (Please note, Cushing’s disease is just one of the numerous causes of Cushing’s syndrome).

    A tumour, outside the pituitary gland, producing ACTH (also called ectopic ACTH tumour).

    Adrenal insufficiency including Addison’s disease (although cortisol levels are low, ACTH levels are raised).

    Congenital adrenal hyperplasia (a genetic disorder with inadequate production of cortisol, aldosterone or both).

    Other chemical compounds secreted with ACTH can also lead to hyper-pigmentation.

    What happens if I have too little adrenocorticotropic hormone?

    Lower than normal levels of adrenocorticotropic hormone may be due to:

    Cushing’s syndrome related to an adrenal tumour.

    Cushing’s syndrome due to steroid medication.

    Conditions affecting the pituitary gland, e.g. hypopituitarism.

    Side-effect of pituitary surgery or radiation therapy.

What is aldosterone?

Aldosterone is a hormone produced in the outer section (cortex) of the adrenal glands, which sit above the kidneys. It plays a central role in the regulation of blood pressure mainly by acting on organs such as the kidney and the colon to increase the amount of salt (sodium) reabsorbed into the bloodstream and to increase the amount of potassium excreted in the urine. Aldosterone also causes water to be reabsorbed along with sodium; this increases blood volume and therefore blood pressure.

How is aldosterone controlled?

Aldosterone is part of a group of linked hormones, which form the renin–angiotensin–aldosterone system. Activation of this system occurs when there is decrease in blood flow to the kidneys following loss of blood volume or a drop in blood pressure (e.g. due to a haemorrhage). Renin is an enzyme that leads to a series of chemical reactions resulting in the production of angiotensin II, which in turn stimulate aldosterone release. Aldosterone causes an increase in salt and water reabsorption into the bloodstream from the kidney thereby increasing the blood volume, restoring salt levels and blood pressure.

What happens if I have too much aldosterone?

The most common cause of high aldosterone levels is excess production, frequently from a small benign adrenal tumour (primary hyperaldosteronism). The symptoms include high blood pressure, low blood levels of potassium and an abnormal increase in blood volume.

What happens if I have too little aldosterone?

Low aldosterone levels are found in a rare condition called Addison’s disease. In Addison’s disease, there is a general loss of adrenal function resulting in low blood pressure, lethargy and an increase in potassium levels in the blood

Androstenedione is described as a ‘pro-hormone’ because it has few effects itself. Instead, it is important because of the ability of different parts of the body to convert it into the hormones, testosterone and oestrogen, which exert many effects on the body.

In females, the outer part of the adrenal glands (known as the cortex) and the ovaries release androstenedione into the bloodstream where it is converted to provide around half of all testosterone and almost all of the body’s oestrone, a form of oestrogen. Although the testes produce large amounts of androstenedione in males, they secrete little of this into the blood and, instead, rapidly convert it into testosterone within the testes. The adrenal glands also produce androstenedione in men, but this contribution is swamped by the testes’ overwhelming production of the other androgenic hormone, testosterone.

How is androstenedione controlled?

Due to its secretion from a number of different glands and its often rapid conversion to other hormones, the control of androstenedione within the body is very complex. However, two key parts of the brain (the hypothalamus and pituitary gland) are known to be important in the control of androstenedione secretion from the testes, ovaries and adrenal cortex. The release of androstenedione by the adrenal cortex is thought to be related to the pituitary gland’s secretion of a specialised hormone, adrenocorticotropic hormone. Precisely how adrenocorticotropic hormone and other hormones control the adrenal gland’s production of androstenedione is, however, unclear. The testes and ovaries are stimulated to release androstenedione by luteinising hormone and follicle stimulating hormone. These are released from the anterior pituitary gland in response to a hormone signal from the hypothalamus.

What happens if I have too much androstenedione?

The effects of too much androstenedione are likely to result from its conversion in the body to oestrogen or testosterone.

In men, too much androstenedione may lead to an imbalance in oestrogen and testosterone production, leading to changes such as breast development. Depending on the cause of the excess androstenedione, other changes, such as the testes becoming smaller, might also occur.

In women, excess body and facial hair growth (called hirsutism), stopping of periods (amenorrhoea), worsening acne and changes to the genitalia may result from too much androstenedione.

Although androstenedione is often abused by bodybuilders in an effort to build muscle bulk, a small number of studies have suggested that its long-term use may actually decrease muscle strength. The precise consequences of having too much androstenendione are, therefore, still unclear.

What happens if I have too little androstenedione?

Boys with too little androstenedione may fail to develop the sexual characteristics associated with puberty, including pubic and body hair, growth of the sexual organs and deepening of the voice. Similarly, girls may fail to start their periods and may not undergo many of the changes usually seen in puberty. In addition, if a male foetus has too little androstenedione, he may be born with abnormal genitalia. Too little androstenedione in later life would cause the same changes for both men and women as too little testosterone and oestrogen.

What is angiotensin?

The liver creates and releases a protein called angiotensinogen. This is then broken up by renin, an enzyme produced in the kidney, to form angiotensin I. This form of the hormone is not known to have any particular biological function in itself but, is an important precursor for angiotensin II. As it passes in the bloodstream through the lungs and kidneys, it is further metabolised to produce angiotensin II by the action of angiotensin-converting enzyme. Following binding to its receptor, found in most tissues of the body, Angiotensin II has effects on:

blood vessels (vascular), to cause constriction (narrowing) of the blood vessels and hence to increase blood pressure

nerves (neurological), to cause the sensation of thirst, desire for salt, and to encourage the release of anti-diuretic hormone from the pituitary gland and noradrenaline from sympathetic nerves

adrenal glands, to stimulate aldosterone production, resulting in the body retaining sodium and losing potassium from the kidneys

the kidneys, to increase sodium retention and to alter the way the kidneys filter blood. This increases water reabsorption in the kidney to increase blood volume and blood pressure.

The overall effect of angiotensin II is to increase blood pressure, body water and sodium content.

How is angiotensin controlled?

An increase in renin production occurs if there is a decrease in sodium levels and a decrease in blood pressure, which is sensed by the kidneys. In addition, low blood pressure can stimulate the sympathetic nervous system to increase renin production, which results in increased conversion of angiotensinogen to angiotensin I, and so the cylce continues. However, since angiotensin I has to be converted to the more active angiotensin II hormone by the angiotensin-converting enzyme, before it can function, this enables control over angiotensin metabolism. The renin–angiotensin system is also activated by other hormones, including corticosteroids, oestrogen and thyroid hormones. On the other hand, natriuretic peptides (produced in the heart and central nervous system) can impede the renin–angiotensin system in order to increase sodium loss in the urine.

What happens if I have too much angiotensin?

Too much angiotensin II is a common problem resulting in excess fluid being retained by the body and, ultimately, raised blood pressure. This often occurs in heart failure where angiotensin is also thought to contribute to growth in the size of the heart. To combat these adverse effects, drugs such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are used in the clinic, although these do have side effects and can lead to excessive retention of potassium (hyperkalaemia).

What happens if I have too little angiotensin?

Control of plasma sodium and potassium concentrations, and the regulation of blood volume and pressure, are all hormonal mechanisms that are impaired by low angiotensin levels. Absence of angiotensin can be associated with retention of potassium, loss of sodium, decreased fluid retention (increased urine output) and low blood pressure.

What is anti-diuretic hormone?

Anti-diuretic hormone is made by special nerve cells found in an area at the base of the brain known as the hypothalamus. The nerve cells transport the hormone down their nerve fibres (axons) to the pituitary gland where the hormone is released into the bloodstream. Anti-diuretic hormone helps to control blood pressure by acting on the kidneys and the blood vessels. Its most important role is to conserve the fluid volume of your body by reducing the amount of water passed out in the urine. It does this by allowing water in the urine to be taken back into the body in a specific area of the kidney. Thus, more water returns to the bloodstream, urine concentration rises and water loss is reduced. Higher concentrations of anti-diuretic hormone cause blood vessels to constrict (become narrower) and this increases blood pressure. A deficiency of body fluid (dehydration) can only be finally restored by increasing water intake.

How is anti-diuretic hormone controlled?

The release of anti-diuretic hormone from the pituitary gland into the bloodstream is controlled by a number of factors. A decrease in blood volume or low blood pressure, which occurs during dehydration or a haemorrhage, is detected by sensors (receptors) in the heart and large blood vessels. These stimulate anti-diuretic hormone release. Secretion of anti-diuretic hormone also occurs if the concentration of salts in the bloodstream increases, for example as a result of not drinking enough water on a hot day. This is detected by special nerve cells in the hypothalamus which simulate anti-diuretic hormone release from the pituitary. If the concentration of salts reaches abnormally low levels, this condition is called hyponatraemia. Anti-diuretic hormone is also released by thirst, nausea, vomiting and pain, and acts to keep up the volume of fluid in the bloodstream at times of stress or injury. Alcohol prevents anti-diuretic hormone release, which causes an increase in urine production and dehydration.

What happens if I have too much anti-diuretic hormone?

High levels of anti-diuretic hormone cause the kidneys to retain water in the body. There is a condition called Syndrome of Inappropriate Anti-Diuretic Hormone secretion (SIADH; a type of hyponatraemia) where excess anti-diuretic hormone is released when it is not needed (see the article on hyponatraemia for more information). With this condition, excessive water retention dilutes the blood, giving a characteristically low salt concentration. Excessive levels of anti-diuretic hormone might be caused by drug side-effects and diseases of the lungs, chest wall, hypothalamus or pituitary. Some tumours (particularly lung cancer), can produce anti-diuretic hormone.

What happens if I have too little anti-diuretic hormone?

Low levels of anti-diuretic hormone will cause the kidneys to excrete too much water. Urine volume will increase leading to dehydration and a fall in blood pressure. Low levels of anti-diuretic hormone may indicate damage to the hypothalamus or pituitary gland, or primary polydipsia (compulsive or excessive water drinking). In primary polydipsia, the low level of anti-diuretic hormone represents an effort by the body to get rid of excess water. Diabetes insipidus is a condition where you either make too little anti-diuretic hormone (usually due to a tumour, trauma or inflammation of the pituitary or hypothalamus), or where the kidneys are insensitive to it. Diabetes insipidus is associated with increased thirst and urine production.

What is anti-Müllerian hormone?

About eight weeks after conception the human fetus has two sets of ducts, one of which can develop into the male reproductive tract and the other into the female reproductive tract. If the fetus is genetically male (XY chromosomes) then the embryonic testes will produce anti-Müllerian hormone. This causes the Müllerian (female) ducts to disappear – hence the term anti-Müllerian hormone, whilst testosterone produced by the testes causes the male (Wollfian) ducts to survive. The Wollfian ducts go on to develop into the different parts of the male reproductive system: the epididymis, the vas deferens, the seminal vesicles and the prostate gland. In a female fetus (XX chromosomes) the Wollfian ducts disappear (because of the lack of testosterone) and the Müllerian ducts develop into the fallopian tubes, uterus (womb), cervix and the upper part of the vagina.

Anti-Müllerian hormone may also have a role in regulating sex steroid production in puberty and in the adult ovaries and testes. In the ovaries, anti-Müllerian hormone appears to be important in the early stages of development of the follicles, which contain and support the eggs prior to fertilisation. The more ovarian follicles a woman has, the more anti-Müllerian hormone her ovaries can produce, and so AMH can be measured in the bloodstream to assess how many follicles a woman has left in her ovaries: her ‘ovarian reserve’.

How is anti-Müllerian hormone controlled?

It is not currently known how the production of anti-Müllerian hormone is controlled.

What happens if I have too much or too little anti-Müllerian hormone?

When the male fetus does not produce enough anti-Müllerian hormone, the Müllerian ducts do not disappear and this leads to persistent Müllerian duct syndrome. Patients with this syndrome will have a male appearance but they usually have undescended testes (cryptorchidism) and low or absent sperm count due to abnormal development of the Wollfian duct. This can be associated with malformation of the vas deferens and epididymis. This condition is rare.

Since ovarian follicles produce anti-Müllerian hormone in adulthood, measuring the levels of anti-Müllerian hormone in blood provides a way of estimating ovarian reserve in women. Consequently, anti-Müllerian hormone levels are routinely used to predict how well a woman is likely to respond to ovarian stimulation for in vitro fertilisation (IVF) fertility treatment, and what doses of hormones should be used during IVF.

In women anti-Müllerian hormone levels peak around puberty and remain relatively constant until after the menopause, when no follicles remain, and levels of anti-Müllerian hormone become low. Some studies suggest that levels of anti-Müllerian hormone may be lower than normal in women who undergo premature ovarian failure. However, anti-Müllerian hormone results need to be interpreted with caution since many other factors can affect an individual’s fertility.

High levels of anti-Müllerian hormone may be associated with polycystic ovary syndrome. However, measuring anti-Müllerian hormone can be misleading and does not give a definitive diagnosis of either premature ovarian failure or polycystic ovary syndrome. It is important that any test to measure anti-Müllerian hormone levels is carried out by a qualified medical professional.

What is calcitonin?

Calcitonin is a hormone that is produced in humans by the parafollicular cells (commonly known as C-cells) of the thyroid gland. Calcitonin is involved in helping to regulate levels of calcium and phosphate in the blood, opposing the action of parathyroid hormone. This means that it acts to reduce calcium levels in the blood. However, the importance of this role in humans is unclear, as patients who have very low or very high levels of calcitonin show no adverse effects.

Calcitonin reduces calcium levels in the blood by two main mechanisms:

It inhibits the activity of osteoclasts, which are the cells responsible for breaking down bone. When bone is broken down, the calcium contained in the bone is released into the bloodstream. Therefore, the inhibition of the osteoclasts by calcitonin directly reduces the amount of calcium released into the blood. However, this inhibition has been shown to be short-lived.

It can also decrease the resorption of calcium in the kidneys, again leading to lower blood calcium levels.

Manufactured forms of calcitonin have, in the past, been given to treat Paget’s disease of bone and sometimes hypercalcaemia and bone pain. However, with the introduction of newer drugs, such as bisphosphonates, their use is now very limited.

How is calcitonin controlled?

The secretion of both calcitonin and parathyroid hormone is determined by the level of calcium in the blood. When levels of calcium in the blood increase, calcitonin is secreted in higher quantities. When levels of calcium in the blood decrease, this causes the amount of calcitonin secreted to decrease too.

The secretion of calcitonin is also inhibited by the hormone somatostatin, which can also be released by the C-cells in the thyroid gland.

What happens if I have too much calcitonin?

There does not seem to be any direct deleterious effect on the body as a result of having too much calcitonin.

Medullary thyroid cancer is a rare type of cancer that arises from the C-cells in the thyroid gland that secrete calcitonin. It is sometimes associated with multiple endocrine neoplasia type 2a and multiple endocrine neoplasia type 2b. Patients with medullary thyroid cancer have high calcitonin levels in their bloodstream. However, it is important to note that these high calcitonin levels are a consequence of this condition, not a direct causal factor.

What happens if I have too little calcitonin?

There does not seem to be any clinical effect on the body as a result of having too little calcitonin. Patients who have had their thyroid gland removed, and have undetectable levels of calcitonin in their blood, show no adverse symptoms or signs as a result of this.

What is cholecystokinin?

Cholecystokinin is produced by I-cells in the lining of the duodenum and is also released by some neurons in the brain. It acts on two types of receptors found throughout the gut and central nervous system.

The most recognised functions of this hormone are in digestion and appetite. It improves digestion by slowing down the emptying of food from the stomach and stimulating the production of bile in the liver as well as its release from the gall bladder. Bile acts like a detergent making the fat droplets smaller so that enzymes can break it down more easily. Cholecystokinin also increases the release of fluid and enzymes from the pancreas to break down fats, proteins and carbohydrates.

Cholecystokinin seems to be involved with appetite by increasing the sensation of fullness in the short-term, that is, during a meal rather than between meals. It may do this by affecting appetite centres in the brain as well as delaying emptying of the stomach. However, more research is needed to confirm this finding.

There is also evidence to suggest that cholecystokinin may have a role in anxiety and panic disorders. This is an effect of cholecystokinin released in the brain, not an effect of secretion from other parts of the body.

How is cholecystokinin controlled?

Fat and protein in the stomach cause the release of cholecystokinin. Increased blood levels of cholecystokinin can be found 15 minutes after a meal has begun and levels remain raised for three hours afterwards. The release of cholecystokinin is blocked by the hormone somatostatin and by bile acids in the small intestine.

What happens if I have too much cholecystokinin?

There are no known cases of too much cholecystokinin. However, weight loss drugs are currently under development that copy the appetite-reducing actions of cholecystokinin.

What happens if I have too little cholecystokinin?

Some research has been carried out to examine blood levels of cholecystokinin when people are fasting or just after they have eaten. There appears to be evidence of less than average cholecystokinin in very obese people, unlike the levels in obese and slim people. This low level of cholecystokinin may contribute to reduced feelings of fullness and difficulty in losing weight in very obese people. However, more research is needed to confirm this finding. Variations in the cholecystokinin gene itself have been associated with obesity, with an increased risk of 60% if people carry the slightly different form (variant) called cholecystokinin H3. How this happens is currently unclear.

What is corticotrophin-releasing hormone?

Corticotrophin-releasing hormone is secreted by the paraventricular nucleus of the hypothalamus which, among other functions, releases hormones. Corticotrophin-releasing hormone has several important actions. Its main role in the body is as the central driver of the stress hormone system, known as the hypothalamic–pituitary–adrenal axis. Corticotrophin-releasing hormone is given this name because it causes release of adrenocorticotropic hormone from the pituitary gland. Adrenocorticotropic hormone in turn travels in the bloodstream to the adrenal glands, where it causes the secretion of the stress hormone cortisol.

Corticotrophin-releasing hormone also acts on many other areas within the brain where it suppresses appetite, increases anxiety, and improves memory and selective attention. Together, these effects co-ordinate behaviour to develop and fine tune the body’s response to a stressful experience.

Corticotrophin-releasing hormone is also produced throughout pregnancy in increasing amounts by the foetus and the placenta, with the effects of increasing cortisol. Ultimately, it is the high levels of corticotrophin-releasing hormone that, along with other hormones, are thought to start labour.

Finally, in smaller quantities, corticotrophin-releasing hormone is also made by certain white blood cells, where it stimulates swelling or tenderness known as inflammation, particularly of the gut.

How is corticotrophin-releasing hormone controlled?

Corticotrophin-releasing hormone secretion is stimulated by nervous activity within the brain. It follows a natural 24 hour rhythm in non-stressed circumstances, where it is highest at around 8 a.m. and lowest overnight. However, corticotrophin-releasing hormone can also be increased above the normal daily levels by a stressful experience, infection or even exercise. An increase in corticotrophin-releasing hormone leads to higher levels of the stress hormone cortisol which mobilises energy resources needed for dealing with the cause of the stress. High levels of stress hormones over a long period can have negative effects on the body. Because of this, cortisol blocks the continued release of corticotrophin-releasing hormone and switches off the hypothalamus–pituitary–adrenal axis, which is known as a negative feedback loop.

Some effects of corticotrophin-releasing hormone in the brain can also be blocked by leptin, a hormone produced by fat tissue. This may be partly why corticotrophin-releasing hormone can control appetite.

What happens if I have too much corticotrophin-releasing hormone?

Abnormally high corticotrophin-releasing hormone levels are connected with a variety of diseases. Because it stimulates anxiety and suppresses appetite, too much corticotrophin-releasing hormone is suspected of causing nervous problems such as clinical depression, anxiety, sleep disturbances and anorexia nervosa.

In addition, high levels of corticotrophin-releasing hormone may also make certain inflammatory problems worse, including rheumatoid arthritis, psoriasis, ulcerative colitis and Crohn’s disease. Initially this might seem unexpected because raised levels of corticotrophin-releasing hormone in the brain can lead to increased glucocorticoids production, and glucocorticoids have an anti-inflammatory effect. However, research has revealed that when high levels of corticotrophin-releasing hormone occur in tissues outside the brain, they can actually have a powerful inflammatory action. Increased corticotrophin-releasing hormone levels within the joints, skin or gut can therefore make these inflammatory conditions worse or even play a role in their development.

What happens if I have too little corticotrophin-releasing hormone?

Research has shown that people with Alzheimer’s disease have particularly low corticotrophin-releasing hormone levels. Some scientists also suspect that a lack of corticotrophin-releasing hormone might cause chronic fatigue syndrome, sometimes called myalgic encephalomyelitis, where sufferers have problems with sleep, memory and concentration. However, further research is needed into both these topics before this can be confirmed.

During pregnancy, low corticotrophin-releasing hormone production by the foetus or the placenta can result in miscarriage.

Cortisol is a steroid hormone, one of the glucocorticoids, made in the cortex of the adrenal glands and then released into the blood, which transports it all round the body. Almost every cell contains receptors for cortisol and so cortisol can have lots of different actions depending on which sort of cells it is acting upon. These effects include controlling the body’s blood sugar levels and thus regulating metabolism, acting as an anti-inflammatory, influencing memory formation, controlling salt and water balance, influencing blood pressure and helping development of the foetus. In many species cortisol is also responsible for triggering the processes involved in giving birth.

A similar version of this hormone, known as corticosterone, is produced by rodents, birds and reptiles.

How is cortisol controlled?

Blood levels of cortisol vary throughout the day, but generally are higher in the morning when we wake up, and then fall throughout the day. This is called a diurnal rhythm. In people that work at night, this pattern is reversed, so the timing of cortisol release is clearly linked to daily activity patterns. In addition, in response to stress, extra cortisol is released to help the body to respond appropriately.

The secretion of cortisol is mainly controlled by three inter-communicating regions of the body; the hypothalamus in the brain, the pituitary gland and the adrenal gland. This is called the hypothalamic–pituitary–adrenal axis. When cortisol levels in the blood are low, a group of cells in a region of the brain called the hypothalamus releases corticotrophin-releasing hormone, which causes the pituitary gland to secrete another hormone, adrenocorticotropic hormone, into the bloodstream. High levels of adrenocorticotropic hormone are detected in the adrenal glands and stimulate the secretion of cortisol, causing blood levels of cortisol to rise. As the cortisol levels rise, they start to block the release of corticotrophin-releasing hormone from the hypothalamus and adrenocorticotropic hormone from the pituitary. As a result, the adrenocorticotropic hormone levels start to drop, which then leads to a drop in cortisol levels. This is called a negative feedback loop.

What happens if I have too much cortisol?

Too much cortisol over a prolonged period of time can lead to a condition called Cushing’s syndrome. This can be caused by a wide range of factors, such as a tumour that produces adrenocorticotropic hormone (and therefore increases cortisol secretion), or taking certain types of drugs. The symptoms include:

rapid weight gain mainly in the face, chest and abdomen contrasted with slender arms and legs

a flushed and round face

high blood pressure

osteoporosis

skin changes (bruises and purple stretch marks)

muscle weakness

mood swings, which show as anxiety, depression or irritability

increased thirst and frequency of urination.

High cortisol levels over a prolonged time can also cause lack of sex drive and, in women, periods can become irregular, less frequent or stop altogether (amenorrhoea).

In addition, there has been a long-standing association between raised or impaired regulation of cortisol levels and a number of psychiatric conditions such as anxiety and depression. However, the significance of this is not yet clearly understood.

What happens if I have too little cortisol?

Too little cortisol may be due to a problem in the pituitary gland or the adrenal gland (Addison’s disease). The onset of symptoms is often very gradual. Symptoms may include fatigue, dizziness (especially upon standing), weight loss, muscle weakness, mood changes and the darkening of regions of the skin. Without treatment, this is a potentially life-threatening condition.

Urgent assessment by a specialist hormone doctor called an endocrinologist is required when a diagnosis of Cushing’s syndrome or Addison’s disease is suspected.

What is dehydroepiandrosterone?

Dehydroepiandrosterone is a precursor hormone, which means it has little biological effect on its own, but has powerful effects when converted into other hormones such as testosterone and oestradiol. Dehydroepiandrosterone is produced from cholesterol mainly by the outer layer of the adrenal glands, known as the adrenal cortex, although it is also made by the testes and ovaries in small amounts. It circulates in the blood, mainly attached to sulphur as dehydroepiandrosterone sulphate, which prevents the hormone being broken down. In women, dehydroepiandrosterone is an important source of oestrogens in the body – it provides about 75% of oestrogens before the menopause, and 100% of oestrogens in the body after menopause.

Dehydroepiandrosterone production increases from around nine or ten years of age, peaks during the 20s and gradually decreases into old age. Dehydroepiandrosterone is also produced in small amounts by the brain, although its precise role there is not clear.

How is dehydroepiandrosterone controlled?

Dehydroepiandrosterone production is controlled by the brain in a negative feedback loop. This means that when dehydroepiandrosterone levels in the body fall, the system is ‘switched on’ and, as levels rise, it ‘switches off’ again.

The system is ‘switched on’ by corticotrophin-releasing hormone being produced by the hypothalamus. This travels to the anterior pituitary gland and causes it to release adrenocorticotropic hormone into the bloodstream. Both of these hormones cause the adrenal glands to produce dehydroepiandrosterone. When dehydroepiandrosterone levels rise, the body shuts off production by stopping corticotrophin-releasing hormone and adrenocorticotropic hormone.

What happens if I have too much dehydroepiandrosterone?

Women with polycystic ovary syndrome and hirsutism and children with congenital adrenal hyperplasia have higher levels of dehydroepiandrosterone/dehydroepiandrosterone sulphate. In addition, levels may be raised in individuals with cancer of the adrenal glands (adrenal carcinoma).

High levels of dehydroepiandrosterone have also been linked to reducing the risk of depression, cardiovascular disease and even death in some studies. Some experts have suggested dehydroepiandrosterone supplements might overcome age-related decline (a so-called ‘elixir of youth’) but this is not supported by current evidence.

Some athletes and bodybuilders also take dehydroepiandrosterone (an anabolic steroid) to increase muscle mass and strength. Serious side-effects from taking manufactured dehydroepiandrosterone have been reported and it is banned by the World Anti-Doping Agency. However, exercise and calorie-restriction have been shown to increase natural dehydroepiandrosterone levels in the body and may lead to longer life.

Since 2000, dehydroepiandrosterone supplementation in combination with gonadotropins has been used in reproductive medicine as a way to treat female infertility.

What happens if I have too little dehydroepiandrosterone?

Low levels of dehydroepiandrosterone have been linked with shorter lifespan in men but not women. However, the reason for this is not fully understood. Decreased dehydroepiandrosterone levels are associated with increased risk of cardiovascular disease in men with type 2 diabetes mellitus and may also cause a shorter lifespan, although further research is needed to confirm this.

In women, low levels of dehydroepiandrosterone are associated with low libido, reduced bone mineral density and osteoporosis. However, supplementation with commercially available dehydroepiandrosterone is not recommended as there is concern about numerous possible side-effects.

What is dihydrotestosterone?

Dihydrotestosterone is a hormone that stimulates the development of male characteristics (an androgen). It is made through conversion of the more commonly known androgen, testosterone. Almost 10% of the testosterone produced by an adult each day is converted to dihydrotestosterone, by the testes and prostate (in men), the ovaries (in women), the skin and other parts of the body. This figure is much lower before puberty however, and it is thought that the increased dihydrotestosterone production may be responsible for the start of puberty in boys, causing development of the genitals (penis, testes and scrotum) and growth of pubic and body hair. This hormone also causes the prostate to grow and is thought to combine with testosterone causing the expression of male sexual behaviour. Dihydrotestosterone is many times more potent than testosterone, and many of the effects that testosterone has in the body only happen after it is converted to dihydrotestosterone.

Less is known about the importance of dihydrotestosterone in women, but it is known to cause much of the body and pubic hair growth seen in girls after puberty and may help to determine the age at which girls begin puberty.

How is dihydrotestosterone controlled?

The amount of dihydrotestosterone present in the body from day to day depends on the amount of testosterone present. When levels of testosterone increase, more of it is converted to dihydrotestosterone and so levels of dihydrotestosterone therefore also increase as a result.

Control of dihydrotestosterone levels in the body is therefore achieved through control of testosterone production, which is controlled by the hypothalamus and the pituitary gland. In response to decreasing levels of testosterone (and therefore reduced amounts of dihydrotestosterone), the hypothalamus releases gonadotrophin-releasing hormone, which travels to the pituitary gland, stimulating it to produce and release luteinising hormone into the bloodstream. Luteinising hormone in the blood then travels to the Leydig cells in the testes in men (or ovaries in women) and stimulates them to produce more testosterone. As testosterone in the blood increases, more of it is also converted to dihydrotestosterone, resulting in higher levels of dihydrotestosterone as well.

As blood levels of testosterone and dihydrotestosterone increase, this feeds back to suppress the production of gonadotrophin-releasing hormone from the hypothalamus which, in turn, suppresses production of luteinising hormone by the pituitary gland. Levels of testosterone (and thus dihydrotestosterone) begin to fall as a result, so negative feedback decreases and the hypothalamus resumes secretion of gonadotrophin-releasing hormone.

What happens if I have too much dihydrotestosterone?

Too much dihydrotestosterone, often resulting from excess testosterone production, has variable effects on men and women. It is unlikely that levels of dihydrotestosterone will be raised before the start of puberty. It is also unlikely that adult men with too much dihydrotestosterone would undergo recognisable changes. Women with too much dihydrotestosterone may develop increased body, facial and pubic hair growth (called hirsutism), stopping of menstrual periods (amenorrhoea) and increased acne. Abnormal changes to the genitalia may also occur in women with too much dihydrotestosterone.

What happens if I have too little dihydrotestosterone?

Dihydrotestosterone is thought to have fewer effects in women and, as a result, it is believed they are relatively unaffected by having too little dihydrotestosterone. It is possible, however, that the start of puberty may be delayed in girls with too little dihydrotestosterone and the amount of pubic and body hair present in adult females may also be reduced.

In contrast, low levels of dihydrotestosterone in men can have dramatic effects. If there is too little dihydrotestosterone whilst male foetuses are still in the womb, for example, they may not be ‘masculinised’ and their genitalia may seem similar to that seen in girls of the same age. Later, boys with too little dihydrotestosterone may undergo some of the changes usually seen in puberty (such as muscle growth and production of sperm) but will not develop normal body hair growth and genital development.

What is erythropoietin?

 Erythropoeitin testing in sport. Blood sample being tested for the presence of the performance-enhancing hormone erythropoeitin.

Erythropoietin is a hormone that is produced predominantly by specialised cells in the kidney. Once it is made, it acts on red blood cells to protect them against destruction. At the same time it stimulates stem cells of the bone marrow to increase the production of red blood cells.

How is erythropoietin controlled?

Althought the precise mechanisms that control the production of erythropoietin are poorly understood, it is well known that specialised cells in the kidney are capable of detecting and responding to low levels of oxygen through increased production of erythropoietin. When there is sufficient oxygen in the blood circulation, the production of erythropoietin is reduced, but when oxygen levels go down, the production of erythropoietin goes up. This is adaptive because it facilitates the production of more red blood cells to transport more oxygen around the body, thus raising oxygen levels in the tissues. For example, erythropoietin production will go up when moving to a high altitude. This is because the air pressure is lower, the pressure of oxygen is lower and so less oxygen is taken up by the blood therefore stimulating erythropoietin production. In low oxygen states people risk developing hypoxia – oxygen deprivation. Hypoxia can also occur when there is poor ventilation of the lungs such as occurs in emphysema and in cardiovascular disease. The production of erythropoietin decreases in kidney failure and various chronic diseases such as AIDS, certain cancers and chronic inflammatory diseases like rheumatoid arthritis.

What happens if I have too much erythropoietin?

Excess erythropoietin results from chronic low oxygen levels or from rare tumours that produce high levels of erythropoietin. It causes a condition known as polycythaemia which is a high red blood cell count. In many people, polycythaemia does not cause any symptoms. However, there are some general and non-specific symptoms including weakness, fatigue, headache, itching, joint pain and dizziness.

What happens if I have too little erythropoietin?

If you have too little erythropoietin, which is usually caused by chronic kidney disease, there will be fewer red blood cells and you will have anaemia. Erythropoietin has been made synthetically for the treatment of anaemia that results from chronic kidney failure. It is also given to patients with some rarer types of cancer.

Some professional athletes have used this type of erythropoietin (known as blood doping) to improve their performance, particularly to increase endurance. Artificially increasing your erythropoietin levels produces more haemoglobin and red blood cells and therefore improves the amount of oxygen that can be delivered to tissues, particularly muscles. This can improve performance, although this type of doping practice is banned by most professional sport committees.

What is follicle stimulating hormone?

Follicle stimulating hormone is one of the gonadotrophic hormones, the other being luteinising hormone. Both are released by the pituitary gland into the bloodstream. Follicle stimulating hormone is one of the hormones essential to pubertal development and the function of women’s ovaries and men’s testes. In women, this hormone stimulates the growth of ovarian follicles in the ovary before the release of an egg from one follicle at ovulation. It also increases oestradiol production. In men, follicle stimulating hormone acts on the Sertoli cells of the testes to stimulate sperm production (spermatogenesis).

How is follicle stimulating hormone controlled?

The production and release of follicle stimulating hormone is regulated by the levels of a number of circulating hormones released by the ovaries and testes. This system is called the hypothalamic–pituitary–gonadal axis. Gonadotrophin-releasing hormone is released from the hypothalamus and binds to receptors in the anterior pituitary gland to stimulate both the synthesis and release of follicle stimulating hormone and luteinising hormone. The released follicle stimulating hormone is carried in the bloodstream where it binds to receptors in the testes and ovaries. Using this mechanism follicle stimulating hormone, along with luteinising hormone, can control the functions of the testes and ovaries.

In women, when hormone levels fall towards the end of the menstrual cycle, this is sensed by nerve cells in the hypothalamus. These cells produce more gonadotrophin-releasing hormone, which in turn stimulates the pituitary gland to produce more follicle stimulating hormone and luteinising hormone, and release these into the bloodstream. The rise in follicle stimulating hormone stimulates the growth of the follicle in the ovary. With this growth, the cells of the follicles produce increasing amounts of oestradiol and inhibin. In turn, the production of these hormones is sensed by the hypothalamus and pituitary gland and less gonadotrophin-releasing hormone and follicle stimulating hormone will be released. However, as the follicle grows, and more and more oestrogen is produced from the follicles, it simulates a surge in luteinising hormone and follicle stimulating hormone, which stimulates the release of an egg from a mature follicle – ovulation.

Thus, during each menstrual cycle, there is a rise in follicle stimulating hormone secretion in the first half of the cycle that stimulates follicular growth in the ovary. After ovulation the ruptured follicle forms a corpus luteum that produces high levels of progesterone. This inhibits the release of follicle stimulating hormone. Towards the end of the cycle the corpus luteum breaks down, progesterone production decreases and the next menstrual cycle begins when follicle stimulating hormone starts to rise again.

In men, the production of follicle stimulating hormone is regulated by the circulating levels of testosterone and inhibin, both produced by the testes. Follicle stimulating hormone regulates testosterone levels and when these rise they are sensed by nerve cells in the hypothalamus so that gonadotrophin-releasing hormone secretion and consequently follicle stimulating hormone is decreased. The opposite occurs when testosterone levels decrease. This is known as a ‘negative feedback’ control so that the production of testosterone remains steady. The production of inhibin is also controlled in a similar way but this is sensed by cells in the anterior pituitary gland rather than the hypothalamus.

What happens if I have too much follicle stimulating hormone?

Most often, raised levels of follicle stimulating hormone are a sign of malfunction in the ovary or testis. If the gonads fail to create enough oestrogen, testosterone and/or inhibin, the correct feedback control of follicle stimulating hormone production from the pituitary gland is lost and the levels of both follicle stimulating hormone and luteinising hormone will rise. This condition is called hypergonadotrophic-hypogonadism, and is associated with primary ovarian failure or testicular failure. This is seen in conditions such as Klinefelter’s syndrome in men and Turner syndrome in women.

In women, follicle stimulating hormone levels also start to rise naturally in women around the menopausal period, reflecting a reduction in function of the ovaries and decline of oestrogen and progesterone production.

There are very rare pituitary conditions that can raise the levels of follicle stimulating hormone in the bloodstream. This overwhelms the normal negative feedback loop and can (rarely) cause ovarian hyperstimulation syndrome in women. Symptoms of this include enlarging of the ovaries and a potentially dangerous accumulation of fluid in the abdomen (triggered by the rise in ovarian steroid output), which leads to pain in the pelvic area.

What happens if I have too little follicle stimulating hormone?

In women, a lack of follicle stimulating hormone leads to incomplete development at puberty and poor ovarian function (ovarian failure). In this situation ovarian follicles do not grow properly and do not release an egg, thus leading to infertility. Since levels of follicle stimulating hormone in the bloodstream are low, this condition is called hypogonadotrophic-hypogonadism. This is seen in a condition called Kallman’s syndrome, which is associated with a reduced sense of smell.

Sufficient follicle stimulating hormone action is also needed for proper sperm production. In the case of complete absence of follicle stimulating hormone in men, lack of puberty and infertility due to lack of sperm (azoospermia) can occur. Partial follicle stimulating hormone deficiency in men can cause delayed puberty and limited sperm production (oligozoospermia), but fathering a child may still be possible. If the loss of follicle stimulating hormone occurs after puberty, there will be a similar loss of fertility.

What is gastrin?

Gastrin is a hormone that is produced by ‘G’ cells in the lining of the stomach and upper small intestine. During a meal, gastrin stimulates the stomach to release gastric acid. This allows the stomach to break down proteins swallowed as food and absorb certain vitamins. It also acts as a disinfectant and kills most of the bacteria that enter the stomach with food, minimising the risk of infection within the gut.

Additionally, gastrin can stimulate the gallbladder to empty its store of bile and the pancreas to secrete enzymes. Bile and pancreatic enzymes help absorb food in the small intestine.

Gastrin also stimulates growth of the stomach lining and increases the muscle contractions of the gut to aid digestion.

How is gastrin controlled?

Before a meal, the anticipation of eating stimulates nerves within the brain which signal to the stomach and stimulate the release of gastrin. Gastrin release is also stimulated by the stretching of the stomach walls during a meal, the presence of certain foods (particularly proteins) within the stomach cavity and an increase in the pH levels of the stomach (i.e. the stomach becoming less acidic).

The production and release of gastrin is slowed by the hormone somatostatin, which is released when the stomach empties at the end of a meal and when the pH of the stomach becomes too acidic.

What happens if I have too much gastrin?

An excess of gastrin can occur due to a gastrin-secreting tumour (gastrinoma, also known as Zollinger-Ellison syndrome) occurring within the small intestine (specifically within the upper part known as a duodenum) or in the pancreas. In gastrinomas, high levels of gastrin moving around the gut stimulate acid release, leading to stomach and small intestine ulcers that may burst. High levels of stomach acid can also cause diarrhoea because the lining of the small intestine becomes damaged.

High levels of circulating gastrin can also occur when the pH of the stomach is high (i.e. not acidic enough), for example, in pernicious anaemia or atrophic gastritis when the stomach lining is damaged and unable to produce and release acid, and during treatment with antacid drugs.

As gastrin also stimulates growth of the stomach lining, it is thought that high gastrin levels may play a role in the development of certain cancers of the digestive tract. However, this has not been proven.

What happens if I have too little gastrin?

It is rare to have too little gastrin. However, low levels of gastric acid may increase the risk of infection within the gut and may limit the ability of the stomach to absorb nutrients.

What is ghrelin?

Ghrelin is a hormone that is produced and released mainly by the stomach with small amounts also released by the small intestine, pancreas and brain.

Ghrelin has numerous functions. It is termed the ‘hunger hormone’ because it stimulates appetite, increases food intake and promotes fat storage. When administered to humans, ghrelin increases food intake by up to 30%; it circulates in the bloodstream and acts at the hypothalamus, an area of the brain crucial in the control of appetite. Ghrelin has also been shown to act on regions of the brain involved in reward processing such as the amygdala.

Ghrelin also stimulates the release of growth hormone from the pituitary gland, which, unlike ghrelin itself, breaks down fat tissue and causes the build-up of muscle.

Ghrelin also has protective effects on the cardiovascular system and plays a role in the control of insulin release.

How is ghrelin controlled?

Ghrelin levels are primarily regulated by food intake. Levels of ghrelin in the blood rise just before eating and when fasting, with the timing of these rises being affected by our normal meal routine. Hence, ghrelin is thought to play a role in mealtime ‘hunger pangs’ and the need to begin meals. Levels of ghrelin increase when fasting (in line with increased hunger) and are lower in individuals with a higher body weight compared with lean individuals, which suggests ghrelin could be involved in the long-term regulation of body weight.

Eating reduces concentrations of ghrelin. Different nutrients slow down ghrelin release to varying degrees; carbohydrates and proteins restrict the production and release of ghrelin to a greater extent than fats.

Somatostatin also restricts ghrelin release, as well as many other hormones released from the digestive tract.

What happens if I have too much ghrelin?

Ghrelin levels increase after dieting, which may explain why diet-induced weight loss can be difficult to maintain. One would expect higher levels in people with obesity. However, ghrelin levels are usually lower in people with higher body weight compared with lean people, which suggests ghrelin is not a cause of obesity; although there is a suggestion that obese people are actually more sensitive to the hormone. However, more research is needed to confirm this.

Prader-Willi syndrome is a genetic disease in which patients have severe obesity, extreme hunger and learning difficulties. Unlike more common forms of obesity, circulating ghrelin levels are high in Prader-Willi syndrome patients and start before the development of obesity. This suggests that ghrelin may contribute to their increased appetite and body weight.

Ghrelin levels are also high in cachexia and the eating disorder, anorexia nervosa. This may be the body’s way of making up for weight loss by stimulating food intake and fat storage.

What happens if I have too little ghrelin?

Gastric bypass surgery, which involves reducing the size of the stomach, is considered to be the most effective treatment for severe, life-threatening obesity. Patients who lose weight after bypass surgery have been found to have lower ghrelin levels than those who lose weight by other means such as diet and exercise, which may partly explain the long-lasting success of this treatment.

What is glucagon?

Glucagon is a hormone that is involved in controlling blood sugar (glucose) levels. It is produced by the alpha cells, found in the islets of Langerhans, in the pancreas, from where it is released into the bloodstream. The glucagon-secreting alpha cells surround the insulin-secreting beta cells, which reflects the close relationship between the two hormones.

Glucagon’s role in the body is to prevent blood glucose levels dropping too low. To do this, it acts on the liver in several ways:

It stimulates the conversion of stored glycogen (stored in the liver) to glucose, which can be released into the bloodstream. This process is called glycogenolysis.

It promotes the production of glucose from amino acid molecules. This process is called gluconeogenesis.

It reduces glucose consumption by the liver so that as much glucose as possible can be secreted into the bloodstream to maintain blood glucose levels.

Glucagon also acts on adipose tissue to stimulate the breakdown of fat stores into the bloodstream.

How is glucagon controlled?

Glucagon works along with the hormone insulin to control blood sugar levels and keep them within set levels. Glucagon is released to stop blood sugar levels dropping too low (hypoglycaemia), while insulin is released to stop blood sugar levels rising too high (hyperglycaemia).

The release of glucagon is stimulated by low blood glucose, protein-rich meals and adrenaline (another important hormone for combating low glucose). The release of glucagon is prevented by raised blood glucose and carbohydrate in meals, detected by cells in the pancreas.

In the longer-term, glucagon is crucial to the body’s response to lack of food. For example, it encourages the use of stored fat for energy in order to preserve the limited supply of glucose.

What happens if I have too much glucagon?

A rare tumour of the pancreas called a glucagonoma can secrete excessive quantities of glucagon. This can cause diabetes mellitus, weight loss, thrombosis’>venous thrombosis and a characteristic skin rash.

What happens if I have too little glucagon?

Unusual cases of deficiency of glucagon secretion have been reported in babies. This results in severely low blood glucose which cannot be controlled without administering glucagon.

Glucagon can be given by injection to restore blood glucose lowered by insulin (even in unconscious patients). It can increase glucose release from glycogen stores more than insulin can suppress it. The effect of glucagon is limited, so it is very important to eat a carbohydrate meal once the person has recovered enough to eat safely.

What is glucagon-like peptide 1?

Glucagon-like peptide 1 belongs to a family of hormones called the incretins, so-called because they enhance the secretion of insulin. Glucagon-like peptide 1 is a product of a molecule called pre-proglucagon, a polypeptide which is split to produce many hormones, including glucagon. Because they come from the same source, these hormones share some similarities, so are called ‘glucagon-like’. Cells found in the lining of the small intestine (called L-cells) are the major source of glucagon-like peptide 1, although it is also secreted in smaller quantities by the pancreas and the central nervous system. Glucagon-like peptide 1 encourages the release of insulin from the pancreas, increases the volume of cells in the pancreas that produce insulin (beta cells) and holds back glucagon release. Glucagon-like peptide 1 also increases the feeling of fullness during and between meals by acting on appetite centres in the brain and by slowing the emptying of the stomach.

How is glucagon-like peptide 1 controlled?

Food is the main stimulus of glucagon-like peptide 1 release, with increased hormone levels detectable after 10 minutes of starting to eat and remaining raised in the blood circulation for several hours after that. The hormone somatostatin holds back the production of glucagon-like peptide 1.

What happens if I have too much glucagon-like peptide 1?

There are no known cases of too much glucagon-like peptide 1. Recently drugs have been developed to mimic glucagon-like peptide 1 in the blood circulation to improve the control of glucose levels in type-2 diabetes. Levels of glucagon-like peptide 1 are also naturally increased after some types of weight-related surgery, which is thought to contribute to the observed weight loss and improvement of type-2 diabetes in these patients.

What happens if I have too little glucagon-like peptide 1?

It has been suggested that too little glucagon-like peptide 1 released after a meal may increase the likelihood of, or worsen, obesity. Since glucagon-like peptide 1 reduces appetite after a meal, if the body releases less of this hormone, individuals may eat more during a meal and are more likely to snack between meals. Dieting, or natural weight loss, is linked to a decrease in glucagon-like peptide 1. The result may be an increased appetite and tendency to regain weight. However, more research is needed to confirm this.

What is glucose-dependent insulinotropic peptide?

Glucose-dependent insulinotropic peptide is a hormone released from the small intestine that enhances the release of insulin following the intake of food. It is a member of the family of hormones known as the incretins of which the other main member is the hormone glucagon-like peptide 1.

Glucose-dependent insulinotropic peptide is made and secreted mainly from the upper section of the small intestine from a specific type of cell known as the K cell. Its main action occurs in the pancreas where it targets beta cells, which produce insulin. Glucose-dependent insulinotropic peptide stimulates the release of insulin from the beta cells in the pancreas in order to maintain low blood sugar levels after eating. It also increases the production of these cells and reduces the rate at which they break down.

Although this is the main function of glucose-dependent insulinotropic peptide, receptors for glucose-dependent insulinotropic peptide are also found in other organs of the body where it has several other effects:

In the brain – glucose-dependent insulinotropic peptide stimulates the growth of cells that have the ability to divide and eventually develop into nerve cells.

In bone – glucose-dependent insulinotropic peptide increases the formation of bone whilst decreasing bone breakdown.

Fat tissue – glucose-dependent insulinotropic peptide is known to increase the amount of fat in the body by increasing the formation of fat cells.

How is glucose-dependent insulinotropic peptide controlled?

The main trigger for glucose-dependent insulinotropic peptide release is food, in particular fatty foods or those foods that are rich in sugar. Once released into the bloodstream, levels of glucose-dependent insulinotropic peptide do not remain high for very long. It is broken down quite quickly (after about seven minutes) and therefore does not remain in the circulating blood for long. Glucose-dependent insulinotropic peptide release is prevented by the hormone somatostatin, produced in the pancreas and gastrointestinal tract.

What happens if I have too much glucose-dependent insulinotropic peptide?

There are currently no known direct causes of too much glucose-dependent insulinotropic peptide. However, increased levels of glucose-dependent insulinotropic peptide have been linked to both type 2 diabetes mellitus and obesity. In type 2 diabetes mellitus, some patients have increased levels of glucose-dependent insulinotropic peptide but it is not known whether this is a cause or consequence of the condition. In type 2 diabetes mellitus, glucose-dependent insulinotropic peptide does not function as well as it should so it is less efficient at stimulating insulin release. This means patients have high blood sugar (hyperglycaemia), which worsens their existing type 2 diabetes mellitus.

With obesity, scientists believe that by eating too much fatty foods there is an over-production of glucose-dependent insulinotropic peptide meaning that more fat tissue is produced.

What happens if I have too little glucose-dependent insulinotropic peptide?

Currently there are no known consequences of having too little glucose-dependent insulinotropic peptide.

What is gonadotrophin-releasing hormone?

Gonadotrophin-releasing hormone is produced and secreted by specialised nerve cells in the hypothalamus of the brain. It is released into tiny blood vessels that carry this hormone from the brain to the pituitary gland, where it stimulates the production of two more hormones – follicle stimulating hormone and luteinising hormone. These hormones are released into the general circulation and act on the testes and ovaries to initiate and maintain their reproductive functions. Follicle stimulating hormone and luteinising hormone control the levels of hormones produced by the testes and ovaries (such as testosterone, oestradiol and progesterone), and are important in controlling the production of sperm in men and the maturation and release of an egg during each menstrual cycle in women.

How is gonadotrophin-releasing hormone controlled?

During childhood, the levels of gonadotrophin-releasing hormone are extremely low, but as puberty approaches there is an increase in gonadotrophin-releasing hormone, which triggers the onset of sexual maturation.

When the ovaries and testes are fully functional, the production of gonadotrophin-releasing hormone, luteinising hormone and follicle stimulating hormone are controlled by the levels of testosterone (in men) and oestrogens (e.g. oestradiol) and progesterone (in women). If the levels of these hormones rise, the production of gonadotrophin-releasing hormone decreases and vice versa.

There is one exception to this rule; in women, at the midpoint of their menstrual cycle, oestradiol (produced by the follicle in the ovary that contains the dominant egg) reaches a critical high point. This stimulates a large increase in gonadotrophin-releasing hormone secretion and, consequently, a surge of luteinising hormone, which stimulates the release of a mature egg. This process is called ovulation.

What happens if I have too much gonadotrophin-releasing hormone?

It is not known what the effects are of having too much gonadotrophin-releasing hormone. Extremely rarely, pituitary adenomas (tumours) can develop, which increase production of gonadotrophins leading to overproduction of testosterone or oestrogen.

What happens if I have too little gonadotrophin-releasing hormone?

A deficiency of gonadotrophin-releasing hormone in childhood means that the individual does not go through puberty. An example is a rare genetic syndrome known as Kallmann’s syndrome, which causes loss of the development of gonadotrophin-releasing hormone-producing nerve cells, with a consequent loss of pubertal development and sexual maturation. It is more common in men than women and leads to loss of development of the testes or ovaries and infertility.

Any trauma or damage to the hypothalamus can also cause a loss of gonadotrophin-releasing hormone secretion, which will stop the normal production of follicle stimulating hormone and luteinising hormone, causing loss of menstrual cycles (amenorrhoea) in women, loss of sperm production in men, and loss of production of hormones from the testes and ovaries.

What is growth hormone?

Growth hormone is released into the bloodstream from the anterior pituitary gland. The pituitary gland also produces other hormones that have different functions from growth hormone.

Growth hormone acts on many parts of the body to promote growth in children. Once the growth plates in the bones (epiphyses) have fused growth hormone does not increase height. In adults, it does not cause growth but it helps to maintain normal body structure and metabolism, including helping to keep blood glucose levels within set levels.

How is growth hormone controlled?

Growth hormone release is not continuous; it is released in a number of ‘bursts’ or pulses every three to five hours. This release is controlled by two other hormones that are released from the hypothalamus (a part of the brain): growth hormone-releasing hormone, which stimulates the pituitary to release growth hormone, and somatostatin, which inhibits that release.

Growth hormone levels are increased by sleep, stress, exercise and low glucose levels in the blood. They also increase around the time of puberty. Growth hormone release is lowered in pregnancy and if the brain senses high levels of growth hormone or insulin-like growth factors already in the blood.

What happens if I have too much growth hormone?

Not surprisingly, too much growth hormone causes too much growth.

In adults, excessive growth hormone for a long period of time produces a condition known as acromegaly, in which patients have swelling of the hands and feet and altered facial features. These patients also have organ enlargement and serious functional disorders such as high blood pressure, diabetes and heart disease. Over 99% of cases are due to benign tumours of the pituitary gland, which produce growth hormone. This condition is more common after middle-age when growth is complete so affected individuals do not get any taller.

Very rarely, increased growth hormone levels can occur in children before they reach their final height, which can lead to excessive growth of long bones, resulting in the child being abnormally tall. This is commonly known as gigantism (a very large increase in height).

Overproduction of growth hormone is diagnosed by giving a sugary drink and measuring the growth hormone level over the next few hours. The sugar should cause growth hormone production to reduce. However, this does not happen in acromegaly.

What happens if I have too little growth hormone?

Too little growth hormone (deficiency) results in poor growth in children. In adults, it causes a reduced sense of wellbeing, increased fat, increased risk of heart disease and weak heart, muscles and bones. The condition may be present from birth where the cause can be unknown, genetic or due to injury to the pituitary gland (during development or at birth).

Growth hormone deficiency may also develop in adults due to brain injury, a pituitary tumour or damage to the pituitary gland (for example, after brain surgery or radiotherapy for cancer treatment). The main treatment is to replace the growth hormone using injections – either once a day or several times a week.

In the past, growth hormone treatment was stopped at the end of growth. It is now clear that growth hormone contributes to both bone mass and muscle mass reaching the best possible level, as well as reducing fat mass during development to an adult. The specialist is therefore likely to discuss the benefits of continuing growth hormone after growth has completed until age 25 to make sure bone and muscle mass reach the best possible level. Additionally, growth hormone has been linked to a sensation of wellbeing, specifically energy levels. There is evidence that 30-50% of adults with growth hormone deficiency feel tired to a level that impairs their wellbeing. These adults may benefit from lifelong treatment with growth hormone. Taking growth hormone when adult will not result in increased height.

What is growth hormone-releasing hormone?

Growth hormone-releasing hormone is a hormone produced in the hypothalamus. The main role of growth hormone-releasing hormone is to stimulate the pituitary gland to produce and release growth hormone into the bloodstream. This then acts on virtually every tissue of the body to control metabolism and growth. Growth hormone stimulates production of insulin-like growth factor 1in the liver and other organs, and this acts on tissues in the body to control metabolism and growth. In addition to its effect on growth hormone secretion, growth hormone-releasing hormone also affects sleep, food intake and memory.

The action of growth hormone-releasing hormone on the pituitary gland is counteracted by somatostatin, a hormone also produced by the hypothalamus, which prevents growth hormone release.

How is growth hormone-releasing hormone controlled?

In order to maintain a normal balanced hormone production, growth hormone-releasing hormone, somatostatin, growth hormone and insulin-like growth factor 1 levels are regulated by each other. The consequence of growth hormone-releasing hormone action is an increase in the circulating levels of growth hormone and insulin-like growth factor 1 which, in turn, act back on the hypothalamus to prevent growth hormone-releasing hormone production and to stimulate somatostatin secretion. Somatostatin then prevents the release of growth hormone from the pituitary gland and growth hormone-releasing hormone production by the hypothalamus, therefore acting as a powerful suppressor of growth hormone secretion.

Many other factors and physiological conditions such as sleep, stress, exercise and food intake also affect the hypothalamic release of growth hormone-releasing hormone and somatostatin.

What happens if I have too much growth hormone-releasing hormone?

Too much growth hormone-releasing hormone production may be caused by hypothalamic tumours or by tumours located in other parts of the body (ectopic tumours). The consequence of too much growth hormone-releasing hormone is a rise in growth hormone levels in the bloodstream and, in many cases, enlargement of the pituitary gland.

In adults, excessive growth hormone for a long period of time produces a condition known as acromegaly in which patients have swelling of the hands and feet and altered facial features. These patients also have organ enlargement and serious functional disorders such as high blood pressure, diabetes and heart disease. An increase in growth hormone before children reach their final height can lead to excessive growth of long bones, resulting in the child being abnormally tall. This is commonly known as gigantism.

However, in most cases, growth hormone overproduction is caused by pituitary tumours that produce growth hormone; only in very rare occasions is excess growth hormone caused by overproduction of growth hormone-releasing hormone.

What happens if I have too little growth hormone-releasing hormone?

If the hypothalamus produces too little growth hormone-releasing hormone, the production and release of growth hormone from the pituitary gland is impaired, leading to a lack of growth hormone (adult-onset growth hormone deficiency). When a deficiency of growth hormone is suspected, a ‘growth hormone stimulating test’ is performed using growth hormone-releasing hormone or other substances, in order to determine the ability of the pituitary gland to release growth hormone.

Childhood-onset growth hormone deficiency is associated with growth failure and delayed physical maturity. In adults, the most important consequences of reduced growth hormone levels are changes in body structure (decreased muscle and bone mass and increased body fat), tiredness, being less lively and a poor health-related quality of life.

What is human chorionic gonadotrophin?

Photo showing a urine sample that has tested positive for human chorionic gonadotropin (hCG). This hormone is secreted by the placenta in pregnant women.

Human chorionic gonadotrophin is a hormone produced by the cells that surround the growing human embryo; these cells will eventually go on to form the placenta. Human chorionic gonadotrophin can be detected in the urine from 7-9 days post-fertilisation as the embryo attaches and implants in the womb; it forms the basis of most over-the-counter and hospital pregnancy tests (see photo).

During the menstrual cycle, when an egg is released from the ovary at ovulation, the remnants of the ovarian follicle (which enclosed the egg) form a new, temporary ovarian gland called the corpus luteum, which produces the hormone progesterone. If, after two weeks, the ovulated egg remains unfertilised, the corpus luteum stops producing progesterone, and breaks down. Through a feedback mechanism, this signals the pituitary gland to produce follicle stimulating hormone (and to a lesser extent luteinising hormone) to initiate the next menstrual cycle. However, in the event that the ovulated egg is fertilised by sperm and an embryo is conceived, it is vital that the corpus luteum continues to produce progesterone until the placenta is established (the placenta then takes over progesterone production). It is important that the corpus luteum keeps producing progesterone because loss of progesterone leads to shedding of the womb lining (menstruation), which would prevent an embryo from implanting. Human chorionic gonadotrophin is the embryonic hormone that ensures the corpus luteum continues to produce progesterone throughout the first trimester of pregnancy.

As well as maintaining progesterone production from the ovary, human chorionic gonadotrophin may also play a role in making sure the lining of the uterus (endometrium) is ready to receive the implanting embryo. Recent studies have indicated that human chorionic gonadotrophin may help to increase the blood supply to the uterus and be involved in re-shaping the lining of the uterus in preparation for the implanting embryo.

How is human chorionic gonadotrophin controlled?

Human chorionic gonadotrophin is produced by the trophoblast cells which surround the developing embryo at approximately day five of pregnancy. The amount of human chorionic gonadotrophin in the bloodstream doubles every 2-3 days as development of the embryo and placenta continue, and levels peak at around six weeks of pregnancy. Following this peak, levels of human chorionic gonadotrophin fall (although they remain detectable throughout pregnancy). Once the placenta is established, it becomes the main source of progesterone production (around week 12 of pregnancy), and human chorionic gonadotrophin is no longer required to maintain ovarian function. However, human chorionic gonadotrophin may have additional beneficial effects in the latter stages of pregnancy; such roles are currently being investigated by researchers.

What happens if I have too much human chorionic gonadotrophin?

There is no strong evidence that high levels of human chorionic gonadotrophin cause direct negative consequences. Very high levels of human chorionic gonadotrophin are rare but can indicate hyper-proliferation of the placenta (also referred to as hydatidiform moles or molar pregnancies), which can lead to cancer (choriocarcinomas) in some cases. Levels of human chorionic gonadotrophin may also be elevated sometimes in association with some non-pregnancy related cancers (e.g. kidney, breast, lung and gastrointestinal tract). In such cases, levels of human chorionic gonadotrophin in the blood/urine can serve as a tumour marker.

In pregnancy, a link between high levels of human chorionic gonadotrophin and occurrence of Down’s syndrome has also been suggested. Studies have shown that the levels of human chorionic gonadotrophin in a Down’s syndrome pregnancy are approximately twice that of an unaffected pregnancy. However, high levels of human chorionic gonadotrophin do not cause Down’s syndrome (rather it is caused by an extra chromosome at position 21); further research is needed to investigate this link.

What happens if I have too little human chorionic gonadotrophin?

Low levels of human chorionic gonadotrophin can indicate a failing pregnancy. Reduced levels of human chorionic gonadotrophin are often observed in ectopic pregnancies (where the embryo implants outside of the uterus) or in miscarriages.

What is insulin?

A person with diabetes being injected with insulin to regulate their blood sugar levels.

Insulin is a hormone made by an organ located behind the stomach called the pancreas. There are specialised areas within the pancreas called islets of Langerhans (the term insulin comes from the Latin insula that means island). The islets of Langerhans are made up of different type of cells that make hormones, the commonest ones are the beta cells, which produce insulin.

Insulin is then released from the pancreas into the bloodstream so that it can reach different parts of the body. Insulin has many effects but mainly it controls how the body uses carbohydrates found in certain types of food. Carbohydrates  are broken down by the human body to produce a type of sugar called glucose. Glucose is the main energy source used by cells. Insulin allows cells in the muscles, liver and fat (adipose tissue) to take up this glucose and use it as a source of energy so they can function properly. Without insulin, cells are unable to use glucose as fuel and they will start malfunctioning. Extra glucose that is not used by the cells will be converted and stored as fat so it can be used to provide energy when glucose levels are too low. In addition, insulin has several other metabolic effects (such as stopping the breakdown of protein and fat).

How is insulin controlled?

The main actions that insulin has are to allow glucose to enter cells to be used as energy and to maintain the amount of glucose found in the bloodstream within normal levels. The release of insulin is tightly regulated in healthy people in order to balance food intake and the metabolic needs of the body. This is a complex process and other hormones found in the gut and pancreas also contribute to this blood glucose regulation. When we eat food, glucose is absorbed from our gut into the bloodstream, raising blood glucose levels. This rise in blood glucose causes insulin to be released from the pancreas so glucose can move inside the cells and be used. As glucose moves inside the cells, the amount of glucose in the bloodstream returns to normal and insulin release slows down. Proteins in food and other hormones produced by the gut in response to food also stimulate insulin release. Hormones released in times of acute stress, such as adrenaline, stop the release of insulin, leading to higher blood glucose levels to help cope with the stressful event.

Insulin works in tandem with glucagon, another hormone produced by the pancreas. While insulin’s role is to lower blood sugar levels if needed, glucagon’s role is to raise blood sugar levels if they fall too low. Using this system, the body ensures that the blood glucose levels remain within set limits, which allows the body to function properly.

What happens if I have too much insulin?

If a person accidentally injects more insulin than required, e.g. because they expend more energy or eat less food than they anticipated, cells will take in too much glucose from the blood. This leads to abnormally low blood glucose levels (called hypoglycaemia). The body reacts to hypoglycaemia by releasing stored glucose from the liver in an attempt to bring the levels back to normal. Low glucose levels in the blood can make a person feel ill.

The body mounts an initial ‘fight back’ response to hypoglycaemia through a specialised set of of nerves called the sympathetic nervous system. This causes palpitations, sweating, hunger, anxiety, tremor and pale complexion that usually warn the person about the low blood glucose level so this can be treated. However, if the initial blood glucose level is too low or if it is not treated promptly and continues to drop, the brain will be affected too because it depends almost entirely on glucose as a source of energy to function properly. This can cause dizziness, confusion, fits and even coma in severe cases.

Some drugs used for people with type 2 diabetes, including sulphonylureas (e.g. gliclazide) and meglitinides (e.g. repaglinide), can also stimulate insulin production within the body and can also cause hypoglycaemia. The body responds in the same way as if excess insulin has been given by injection.

Furthermore, there is a rare tumour called an insulinoma that occurs with an incidence of 1-4 per million population. It is a tumour of the beta cells in the pancreas. Patients with this type of tumour present with symptoms of hypoglycaemia.

What happens if I have too little insulin?

People with diabetes have problems either making insulin, how that insulin works or both. The main two types of diabetes are type 1 and type 2 diabetes, although there are other more uncommon types.

People with type 1 diabetes produce very little or no insulin at all. This condition is caused when the beta cells that make insulin have been destroyed by antibodies (these are usually substances released by the body to fight against infections), hence they are unable to produce insulin. With too little insulin, the body can no longer move glucose from the blood into the cells, causing high blood glucose levels. If the glucose level is high enough, excess glucose spills into the urine. This drags extra water into the urine causing more frequent urination and thirst. This leads to dehydration, which can cause confusion. In addition, with too little insulin, the cells cannot take in glucose for energy and other sources of energy (such as fat and muscle) are needed to provide this energy. This makes the body tired and can cause weight loss. If this continues, patients can become very ill. This is because the body attempts to make new energy from fat and causes acids to be produced as waste products. Ultimately, this can lead to coma and death if medical attention is not sought. People with type 1 diabetes will need to inject insulin in order to survive.

Type 2 diabetes can be caused by two main factors and its severity will depend on how advanced it is. Firstly, the patient’s beta cells may have problems manufacturing insulin, so although some insulin is produced, it is not enough for the body’s needs. Secondly, the available insulin doesn’t work properly because the areas in the cell where insulin acts, called insulin receptors, become insensitive and stop responding to the insulin in the bloodstream. These receptors appear to malfunction more in people who carry excessive amount of  weight. Some people with type 2 diabetes might initially experience very few symptoms and the raised blood glucose is only picked up when a routine blood test is arranged for another reason; other people might experience symptoms similar to those seen in patients with type 1 diabetes (thirst, frequent urination, dehydration, hunger, fatigue and weight loss). Some patients with type 2 diabetes can control their symptoms by improving their diet and/or losing weight, some will need tablets, and others will need to inject insulin to improve blood glucose levels. See the article on diabetes mellitus for more information.

What is kisspeptin?

Kisspeptin is produced from the hypothalamus and causes a cascade of cell-cell communication, ultimately leading to the production of the hormones, luteinising hormone and follicle stimulating hormone from the pituitary gland, which are released into the blood. These hormones act on testes and ovaries to produce the sex steroids testosterone and oestradiol, which cause the physical and emotional changes that are well characterised during puberty.

Kisspeptin has a non-hormonal role too and was originally named metastin after its ability to prevent the spread of cancer (metastasis).

How is kisspeptin controlled?

Kisspeptin is released together with two other hormones, neurokinin B and dynorphin. Consequently, the nerve cells making kisspeptin, dynorphin and neurokinin B are popularly referred to as KNDy (pronounced ‘candy’). We are currently trying to understand exactly what neurokinin B and dynorphin hormones do, but they appear to control the release of kisspeptin.

What happens if I have too much kisspeptin?

It is not yet clear whether having too much kisspeptin is good or bad, but a few small studies have linked high levels of kisspeptin during childhood to cases of (early) precocious puberty. More research is now needed to determine if this is the case.

What happens if I have too little kisspeptin?

When kisspeptin cannot act properly on its target cells in the body, it causes infertility. A clinical trial has shown that giving kisspeptin to women with infertility and women who do not menstruate (a condition known as amenorrhoea) can restore the hormone levels in these conditions. Furthermore, a clinical trial has recently shown that a single injection of kisspeptin can trigger ovulation (release of eggs), and these eggs can be artificially fertilised, be placed back inside the womb (in vitro fertilisation), and result in successful pregnancy. Further studies are needed to determine whether kisspeptin will offer improvements in fertility therapy over existing treatments for couples with infertility.

Adolescents who have faulty kisspeptin signalling fail to undergo puberty (hypogonadotrophic hypogonadism), although this is a rare condition.

Recent evidence now suggests kisspeptin might play other roles in the body since it is also present outside the brain, e.g. in the placenta and the cardiovascular system. For example, levels of kisspeptin in the blood go up massively (7,000 times!) during pregnancy, although the reason why is not yet understood. Intriguingly, a few studies have shown that women who have less kisspeptin in the bloodstream early on in pregnancy may later develop serious complications such as miscarriage or pre-eclampsia (high blood pressure in the mother, which may cause growth restriction in the unborn baby). It has been suggested by some that measuring kisspeptin during early pregnancy may be a useful screening tool to detect pregnancy complications earlier and hopefully lead to improved care. More research is now needed to determine if this is the case.

What is leptin?

Leptin is a hormone released from fat cells in adipose tissue. Leptin signals to the brain, in particular to an area called the hypothalamus. Leptin does not affect food intake from meal to meal but, instead, acts to alter food intake and control energy expenditure over the long term. Leptin has a more profound effect when we lose weight and levels of the hormone fall. This stimulates a huge appetite and increased food intake. The hormone helps us to maintain our normal weight and unfortunately for dieters, makes it hard to lose those extra pounds!

How is leptin controlled?

Because leptin is produced by fat cells, the amount of leptin released is directly related to the amount of body fat; so the more fat an individual has, the more leptin they will have circulating in their blood. Leptin levels increase if an individual increases their fat mass over a period of time and, similarly, leptin levels decrease if an individual decreases their fat mass over a period of time.

What happens if I have too much leptin?

Obese people have unusually high levels of leptin. This is because in some obese people, the brain does not respond to leptin, so they keep eating despite adequate (or excessive) fat stores, a concept known as ‘leptin resistance’. This causes the fat cells to produce even more leptin. This is similar to the way people with type 2 diabetes have unusually high levels of insulin, as their body is resistant to the effects of insulin. The cause of leptin resistance is still unclear.

What happens if I have too little leptin?

There is an extremely rare condition called congenital leptin deficiency, which is a genetic condition in which the body cannot produce leptin. In the UK, there are only about four families affected by this genetic condition.

Absence of leptin makes the body think it does not have any fat whatsoever and this results in uncontrolled food intake and severe childhood obesity. In addition, leptin deficiency may cause delayed puberty and poor function of the immune system. This condition can be well treated by leptin injections, which cause dramatic weight loss.

What is luteinising hormone?

Luteinising hormone, like follicle stimulating hormone, is a gonadotrophic hormone produced and released by cells in the anterior pituitary gland. It is crucial in regulating the function of the testes in men and ovaries in women.

In men, luteinising hormone stimulates Leydig cells in the testes to produce testosterone, which acts locally to support sperm production. Testosterone also exerts effects all around the body to generate male characteristics such as increased muscle mass, enlargement of the larynx to generate a deep voice, and the growth of facial and body hair.

In women, luteinising hormone carries out different roles in the two halves of the menstrual cycle. In weeks one to two of the cycle, luteinising hormone is required to stimulate the ovarian follicles in the ovary to produce the female sex hormone, oestradiol. Around day 14 of the cycle, a surge in luteinising hormone levels causes the ovarian follicle to tear and release a mature oocyte (egg) from the ovary, a process called ovulation. For the remainder of the cycle (weeks three to four), the remnants of the ovarian follicle form a corpus luteum. Luteinising hormone stimulates the corpus luteum to produce progesterone, which is required to support the early stages of pregnancy, if fertilisation occurs.

How is luteinising hormone controlled?

The secretion of luteinising hormone from the anterior pituitary gland is regulated through a system called the hypothalamic-pituitary-gonadal axis. Gonadotrophin-releasing hormone is released from the hypothalamus and binds to receptors in the anterior pituitary gland to stimulate both the synthesis and release of luteinising hormone (and follicle stimulating hormone). The released luteinising hormone is carried in the bloodstream where it binds to receptors in the testes and ovaries to regulate their hormone secretions and the production of sperm or eggs.

The release of hormones from the gonads can suppress the secreton of gonadotrophin-releasing hormone and, in turn, luteinising hormone from the anterior pituitary gland. When levels of hormones from the gonads fall, the reverse happens and gonadtrophin-releasing hormone and hence luteinising hormone rise. This is known as negative feedback.

In men, testosterone exerts this negative feedback and in women oestrogen and progesterone exert the same effect except at the midpoint in the menstrual cycle. At this point, high oestrogen secretions from the ovary stimulate a surge of luteinising hormone from the pituitary gland, which triggers ovulation.

The fine tuning of luteinising hormone release is vital to maintaining fertility. Because of this, compounds designed to mimic the actions of gonadotrophin-releasing hormone, luteinising hormone and follicle stimulating hormone are used to stimulate gonadal function in assisted conception techniques such as in vitro fertilisation (IVF). Measuring the levels of luteinising hormone present in urine can be used to predict the timing of the luteinising hormone surge in women, and hence ovulation. This is one of the methods employed in ovulation prediction kits used by couples wishing to conceive.

What happens if I have too much luteinising hormone?

Too much luteinising hormone can be an indication of infertility. Since the secretion of luteinising hormone is tightly controlled by the hypothalamic-pituitary-gonadal axis, high levels of luteinising hormone in the bloodstream can indicate decreased sex steroid production from the testes or ovaries (for example, as in premature ovarian failure).

Polycystic ovary syndrome is a common condition in women associated with high levels of luteinising hormone and reduced fertility. In this condition, an imbalance between luteinising hormone and follicle stimulating hormone can stimulate inappropriate production of testosterone.

Genetic conditions, such as Klinefelter’s syndrome and Turner syndrome, can also result in high luteinising hormone levels. Klinefelter’s syndrome is a male-only disorder and results from carrying an extra X chromosome (so that men have XXY, rather than XY chromosomes). As a result of this, the testes are small and do not secrete adequate levels of testosterone to support sperm production. Turner syndrome is a female-only disorder caused by a partial or full deletion of an X chromosome (so that women have XO, rather than XX). In affected patients, ovarian function is impaired and therefore luteinising hormone production increases to try to stimulate ovarian function.

What happens if I have too little luteinising hormone?

Too little luteinising hormone will also result in infertility in both men and women, as a critical level of luteinising hormone is required to support testicular or ovarian function.

In men, an example of a condition where low levels of luteinising hormone are found is Kallmann’s syndrome, which is associated with a deficiency in gonadotrophin-releasing hormone secretion from the hypothalamus.

In women, a lack of luteinising hormone means that ovulation does not occur and menstrual periods may not occur regularly. An example of a condition which can be caused by too little luteinising hormone is amenorrhoea.

What is melanocyte-stimulating hormone?

Melanocyte-stimulating hormone is a collective name for a group of peptide hormones produced by the skin, pituitary gland and hypothalamus. In response to ultraviolet (UV) radiation its production by the skin and pituitary is enhanced, and this plays a key role in producing coloured pigmentation found in the skin, hair and eyes. It does this by inducing specialised skin cells called melanocytes to produce a pigment called melanin; melanin protects cells from DNA-(1)’>DNA damage, which can lead to skin cancer (melanoma).

Melanocyte-stimulating hormone is produced from the same precursor molecule as adrenocorticotropic hormone called pro-opiomelanocortin (POMC).

Although named for its stimulatory effect on pigment cells, melanocyte-stimulating hormone produced in the hypothalamus can also suppress appetite by acting on receptors in the hypothalamus in the brain. This effect is enhanced by leptin, a hormone released from fat cells.

Melanocyte-stimulating hormone also affects a range of other processes in the body; it has anti-inflammatory effects, can influence the release of the hormone aldosterone, which controls salt and water balance in the body, and also has an effect on sexual behaviour.

How is melanocyte-stimulating hormone controlled?

Melanocyte-stimulating hormone secretion from the pituitary is increased by exposure to UV light. Unlike most hormones, melanocyte-stimulating hormone release is not thought to be controlled by a direct feedback mechanism.

What happens if I have too much melanocyte-stimulating hormone?

A direct consequence of high levels of melanocyte-stimulating hormone is increased production of melanin. This can occur as a result of prolonged exposure to the sun or skin tanning. However, people with a high blood level of melanocyte-stimulating hormone do not necessarily tan very well or have even skin pigmentation. Very fair-skinned people tend to produce less melanin due to variations in their melanocyte-stimulating hormone receptors, which means they do not respond to melanocyte-stimulating hormone levels in the blood.

Hyperpigmentation or abnormal darkening of the skin is found in patients with primary adrenal insufficiency (Addison’s disease). In Addison’s disease, the adrenal glands do not produce enough hormones (including cortisol). As a consequence, the hypothalamus stimulates the pituitary gland to release more adrenocorticotropic hormone to try and stimulate the adrenal glands to produce more cortisol. Adrenocorticotropic hormone can be broken down to produce melanocyte-stimulating hormone, leading to hyperpigmentation of the skin.

Melanocyte-stimulating hormone levels are also raised during pregnancy and in women using birth control pills, which can cause hyperpigmentation of the skin. Cushing’s syndrome, due to an excess production of adrenocorticotropic hormone, can also lead to hyperpigmentation.

What happens if I have too little melanocyte-stimulating hormone?

A deficiency in melanocyte-stimulating hormone results in a lack of skin pigmentation and subsequent loss of natural protection from UV rays of the sun. In secondary adrenal insufficiency, damage to the pituitary gland prevents release of adrenocorticotropic hormone and melanocyte-stimulating hormone and there is reduced pigmentation of the skin. Melanocyte-stimulating hormone deficiency can cause increased inflammation, pain, and sleeping problems, as well as a reduction in the levels of anti-diuretic hormone, which causes thirst and frequent urination. Melanocyte-stimulating hormone deficiency may also result in increased food intake and obesity.

What is melatonin?

The production and release of melatonin from the pineal gland occurs with a clear daily (circadian) rhythm, with peak levels occurring at night. Once produced, it is secreted into the blood stream and cerebrospinal fluid (the fluid around the brain & spinal cord) and conveys signals to distant organs. Melatonin is carried by the circulation from the brain to all areas of the body. Tissues expressing proteins called receptors specific for melatonin are able to detect the peak in circulating melatonin at night and this signals to the body that it is night-time. Night-time levels of melatonin are at least 10-fold higher than daytime concentrations.

In addition to its circadian rhythm, melatonin levels also have a seasonal (or circannual) rhythm, with higher levels in the autumn and winter, when nights are longer, and lower levels in the spring and summer.

In many animals (including a wide range of mammals and birds), melatonin from the pineal gland is essential for the regulation of the body’s seasonal biology (e.g. reproduction, behaviour and coat growth) in response to changing day length. The importance of pineal melatonin in human biology is not clear, although it may help to synchronise circadian rhythms in different parts of the body.

In humans, nocturnal levels of melatonin decrease across puberty. The level of circulating melatonin can be detected in samples of blood and saliva, and this is used in clinical research to identify internal circadian rhythms.

Most of the research into the function of the pineal gland involves the human brain’s responses to melatonin rhythms. The evidence supports two roles for melatonin in humans: the involvement of nocturnal melatonin secretion in initiating and maintaining sleep, and control by the day/night melatonin rhythm of the timing of other 24-hour rhythms. Melatonin has, therefore, often been referred to as a ‘sleep hormone’; although it is not essential for human sleep, we sleep better during the time that melatonin is secreted.

Association between tumours of the pineal gland and the timing of puberty suggests that melatonin may also have a minor role in reproductive development, although the mechanism of this action is uncertain. Melatonin secretion by the human pineal gland varies markedly with age. Melatonin secretion starts during the third or fourth months of life and coincides with the consolidation of night-time sleep. Following a rapid increase in secretion, nocturnal melatonin levels peak at ages one to three years, then decline slightly to a plateau that persists throughout early adulthood. After a steady decline in most people, night-time levels of melatonin in a 70-year old are only a quarter or less of those seen in young adults.

Night-time melatonin secretion is suppressed by a relatively dim light when pupils are dilated. This has been suggested as the main way through which prolonged use of devices such as laptops and smartphones before bedtime can have a negative impact on melatonin secretion, circadian rhythms and sleep.

In addition to its production in the body, melatonin can also be taken in capsule form. The clinical uses of melatonin include treatment of age-associated insomnia, jet lag, and shift work. When administered at an appropriate time of day, it can reset the body’s circadian rhythms (see the articles on jet lag and circadian rhythm sleep disorders). This resetting effect of melatonin has been reported for many dose strengths, including those that are equivalent to the concentration of melatonin naturally produced by the pineal gland. Higher doses of melatonin can reset circadian rhythms, bring on sleepiness and lower core body temperature.

How is melatonin controlled?

In humans and other mammals, the daily rhythm of pineal melatonin production is driven by the ‘master’ circadian clock. This ‘clock’ is in a region of the brain called the suprachiasmatic nuclei, which expresses a series of genes termed clock genes that continuously oscillate throughout the day. This is synchronised to the solar day via light input from the eyes. The suprachiasmatic nuclei link to the pineal gland through a complex pathway in the nervous system, passing through different brain areas, into the spinal cord and then finally reaching the pineal gland. During the day, the suprachiasmatic nuclei stops melatonin production by sending inhibitory messages to the pineal gland. At night however, the suprachiasmatic nuclei are less active, and the inhibition exerted during the day is reduced resulting in melatonin production by the pineal gland.

Light is an important regulator of melatonin production from the pineal gland. Firstly, it can reset a specific area of the brain (the suprachiasmatic nuclei clock) and, as a result, the timing of the melatonin production. Secondly, exposure to light during the body’s biological night reduces melatonin production and release.

What happens if I have too much melatonin?

There are large variations in the amount of melatonin produced by individuals and these are not associated with any health problems. The main consequences of swallowing large amounts of melatonin are drowsiness and reduced core body temperature. Very large doses have effects on the performance of the human reproductive system. There is also evidence that very high concentrations of melatonin have an antioxidant effect, although the purpose of this has not yet been established.

What happens if I have too little melatonin?

Reduced melatonin production is not known to have any effect on health.

What is oestradiol?

Oestradiol is a steroid hormone made from cholesterol and is the strongest of the three naturally produced oestrogens. It is the main oestrogen found in women and has many functions, although it mainly acts to mature and maintain the female reproductive system. A natural increase in blood oestradiol concentrations during the menstrual cycle causes an egg to mature and be released; that is, to be ovulated. Another important role of oestradiol is to thicken the lining of the uterus so that the egg can implant if it becomes fertilised. Oestradiol also promotes development of breast tissue and increases both bone and cartilage density.

In premenopausal women, oestradiol is mostly made by the ovaries. Oestradiol levels vary throughout the monthly menstrual cycle, being highest at ovulation and lowest at menstruation. Oestradiol levels in women reduce slowly with age, with a large decrease occurring at the menopause when the ovaries ‘switch off’. In pregnant women, the placenta also produces a lot of oestradiol especially towards the end of the pregnancy.

Men also produce oestradiol; however, the amounts produced are much lower than in women. Within the testes, some testosterone is changed into oestradiol and this oestradiol is essential for the production of sperm. In both sexes, oestradiol is also made in much smaller amounts by fat tissue, the brain and the walls of blood vessels.

How is oestradiol controlled?

The production of oestradiol in women’s ovaries is controlled by hormones released from both the hypothalamus in the brain and the pituitary: this is called the reproductive axis in the female and is also known as the hypothalamic–pituitary–ovarian (or gonadal) axis. The hypothalamus in the base of the brain releases a hormone called gonadotropin-releasing hormone. Gonadotropin-releasing hormone then acts on the pituitary gland to cause the release of two further hormones, luteinising hormone (LH) and follicle stimulating hormone (FSH). LH and FSH enter the blood and stimulate the ovary; in particular, LH and FSH act on the cells that surround each egg (these cells plus the egg form a unit called a follicle) stimulating the follicle to grow and develop. In the last stages of growth and development the cells surrounding the egg will produce oestradiol. After the egg has been ovulated, the ovulated follicle will become a corpus luteum. The corpus luteum produces both progesterone and oestradiol and the primary role of these two hormones is to ensure that the lining of the uterus is fully prepared for implantation, if fertilisation occurs. The amount of oestradiol (and progesterone) in the circulation communicates with the hypothalamus and pituitary to control the development of an egg, ovulation and the menstrual cycle.

What happens if I have too much oestradiol?

In women, too much oestradiol can have a number of effects. In mild cases, excess oestradiol may cause acne, constipation, loss of libido and depression. More severe effects can include, weight gain, female infertility, stroke, heart attack and an increased risk of developing uterine and/or breast cancer.

In men, too much oestradiol can also cause sexual dysfunction, loss of muscle tone, increased body fat and the development of female characteristics, such as breast tissue. Oestradiol becomes more dominant as a man ages and his testosterone production reduces, which scientists think may be a contributing factor in the development of prostate cancer.

The combined oral contraceptive pill (the pill) contains synthetic forms of both progesterone and oestradiol. The pill works by preventing ovulation, making it nearly 100% effective in preventing pregnancy. As well as preventing ovulation, the synthetic hormones make the cervical mucus thicker and therefore more difficult for the sperm to move through, thereby reducing their chances of getting to the uterus and oviducts. The synthetic oestradiol was added to prevent breakthrough bleeding, which sometimes occurs with the progesterone-only pill (the mini pill).

What happens if I have too little oestradiol?

Oestradiol is necessary for bone development, so people with low oestradiol tend to have skeletal problems like inadequate bone growth and osteoporosis. Girls will also encounter problems at puberty such as a delay in, or failure of, breast development, a disrupted or absent menstrual cycle and infertility. Oestradiol also has important roles in the brain, where low levels can cause depression, fatigue and mood swings.

A woman’s oestradiol production falls naturally at the menopause and causes many of its symptoms. Initially these include night sweats, hot flushes, vaginal dryness and mood swings, while in the long term she is more likely to develop osteoporosis. Oestradiol is used in hormone replacement therapy to relieve these symptoms of the menopause in women. There are many recognised pros and cons to hormone replacement therapy. See the articles on menopause and ‘What is HRT?’ for more information.

What is oestriol?

Oestriol is one of three oestrogens naturally produced by women. Normally, levels in the body are very low, but during pregnancy, it is made in much higher amounts by the placenta. Oestriol levels increase throughout pregnancy and are highest just before birth. It is an indicator of the health of the unborn fetus because the chemical from which it is made in the placenta, comes from another chemical which is first made in the baby’s adrenal glands and then gets altered in the liver of the baby before being finally converted to oestriol in the placenta. It causes growth of the uterus and increases its sensitivity to other pregnancy-related hormones, thus causing a gradual preparation for birth. Oestriol levels start to increase from week eight of pregnancy and scientists now think that labour begins when oestriol becomes the dominant hormone.

How is oestriol controlled?

Oestriol is made by the placenta from a chemical that comes from the fetus. The fetal adrenal glands first make a hormone called dehydroepiandrosterone sulphate (DHEAS). DHEAS is then transported to the fetal liver and made into 16a-hydroxy-DHEAS. The 16a-hydroxy-DHEAS is in turn transported to the placenta where it is then made into oestriol. For most of pregnancy, most of the oestriol made is bound to other chemicals thereby preventing the oestriol from exerting any biological effects.

What happens if I have too much oestriol?

A sudden surge in oestriol happens around three weeks before labour. If the surge comes early, this can suggest a premature birth.

Some hormone replacement therapy (HRT) preparations contain oestriol. Although the body removes oestriol much faster than other oestrogens, there are positives and negatives to its use in HRT. See the articles on menopause and What is HRT? for more information.

What happens if I have too little oestriol?

In non-pregnant women, oestriol only exists at very low levels. Too little unbound oestriol during pregnancy can indicate that there are problems with the baby, such as Down’s syndrome, or problems with the placenta. Later in pregnancy, comparatively low oestriol indicates that labour may not come on its own, but will have to be induced.

Future uses

In some pregnant women with autoimmune diseases, it has been observed that their symptoms are not as severe during their pregnancy, especially the later stages of pregnancy when oestriol levels are highest. Based on these observations some researchers are investigating whether oestriol is able to suppress the immune system and therefore if it could be used to relieve some of the symptoms of conditions such as multiple sclerosis and rheumatoid arthritis.

What is oestrone?

Oestrone is one of three types of oestrogen made by the body. The other types of oestrogen are called oestradiol and oestriol. Oestrone is primarily produced by the ovaries as well as by adipose tissue and the adrenal glands. It has a much weaker biological activity than oestradiol. Oestrone is the major type of oestrogen hormone produced in any quantities in postmenopausal women.

How is oestrone controlled?

Very little is known about how the production of oestrone is controlled. In premenopausal women, about 50% of oestrone is produced by the ovaries. The remaining 50% is produced by fat tissue and the adrenal glands, which are also the sources of oestrone in children, men and postmenopausal women. Because oestrone is less active than oestradiol, it is thought that oestrone may act as a reservoir that can be converted into oestradiol as needed.

What happens if I have too much oestrone?

Increased oestrone production can occur in women with breast cancer and in men undergoing treatment for testicular or prostate cancer (which reduces testosterone production). Obese women also produce more oestrone from their fat tissues. Overproduction of oestrone may be associated with the development of breast and endometrial cancer in women. Aside from this oestrone production may affect health in both positive and negative ways, but the full extent of this is currently not known.

What happens if I have too little oestrone?

Low levels of oestrogens cause osteoporosis, fatigue, hot flushes, loss of libido and depression. As oestrone is the main oestrogen in postmenopausal women, it is thought that low levels may worsen these symptoms (which are also common during the menopause), particularly in the case of osteoporosis. However, further research is needed to confirm this.

What is oxytocin?

Oxytocin is produced in the hypothalamus and is secreted into the bloodstream by the posterior pituitary gland. Secretion depends on electrical activity of neurons in the hypothalamus – it is released into the blood when these cells are excited.

The two main actions of oxytocin in the body are contraction of the womb (uterus) during childbirth and lactation. Oxytocin stimulates the uterine muscles to contract and also increases production of prostaglandins, which increase the contractions further. Manufactured oxytocin is sometimes given to induce labour if it has not started naturally or it can be used to strengthen contractions to aid childbirth. In addition, manufactured oxytocin is often given to speed up delivery of the placenta and reduce the risk of heavy bleeding by contracting the uterus. During breastfeeding, oxytocin promotes the movement of milk into the breast, allowing it to be excreted by the nipple. Oxytocin is also present in men, playing a role in sperm movement and production of testosterone by the testes.

More recently, oxytocin has been suggested to be an important player in social behaviour.

In the brain, oxytocin acts as a chemical messenger and has been shown to be important in human behaviours including sexual arousal, recognition, trust, anxiety and mother–infant bonding. As a result, oxytocin has been called the ‘love hormone’ or ‘cuddle chemical’.

Many research projects are undertaken, looking at the role of oxytocin in addiction, brain injury, anorexia and stress, among other topics.

How is oxytocin controlled?

Oxytocin is controlled by a positive feedback mechanism where release of the hormone causes an action that stimulates more of its own release. When contraction of the uterus starts, for example, oxytocin is released, which stimulates more contractions and more oxytocin to be released. In this way, contractions increase in intensity and frequency.

There is also a positive feedback involved in the milk-ejection reflex. When a baby sucks at the breast of its mother, the stimulation leads to oxytocin secretion into the blood, which then causes milk to be let down into the breast. Oxytocin is also released into the brain to help stimulate further oxytocin secretion. These processes are self-limiting; production of the hormone is stopped after the baby is delivered or when the baby stops feeding.

What happens if I have too much oxytocin?

At present, the implications of having too much oxytocin are not clear. High levels have been linked to benign prostatic hyperplasia, a condition which affects the prostate in more than half of men over the age of 50. This may cause difficulty in passing urine.

It may be possible to treat this condition by manipulating oxytocin levels; however, more research is needed before any possible treatments are available.

What happens if I have too little oxytocin?

Similarly, it is not fully understood at present if there are any implications of having too little oxytocin in the body. A lack of oxytocin in a nursing mother would prevent the milk-ejection reflex and prevent breastfeeding.

Low oxytocin levels have been linked to autism and autistic spectrum disorders (e.g. Asperger syndrome) – a key element of these disorders being poor social functioning. Some scientists believe oxytocin could be used to treat these disorders. In addition, low oxytocin has been linked to depressive symptoms and it has been proposed as a treatment for depressive disorders. However, there is not enough evidence at present to support its use for any of these conditions.

What is parathyroid hormone?

The parathyroid glands are located in the neck, just behind the butterfly-shaped thyroid gland.

Parathyroid hormone is secreted from four parathyroid glands, which are small glands in the neck, located behind the thyroid gland. Parathyroid hormone regulates calcium levels in the blood, largely by increasing the levels when they are too low. It does this through its actions on the kidneys, bones and intestine:

Bones – parathyroid hormone stimulates the release of calcium from large calcium stores in the bones into the bloodstream. This increases bone destruction and decreases the formation of new bone.

Kidneys – parathyroid hormone reduces loss of calcium in urine. Parathyroid hormone also stimulates the production of active vitamin D in the kidneys.

Intestine – parathyroid hormone indirectly increases calcium absorption from food in the intestine, via its effects on vitamin D metabolism.

How is parathyroid hormone controlled?

Parathyroid hormone is mainly controlled by the negative feedback of calcium levels in the blood to the parathyroid glands. Low calcium levels in the blood stimulate parathyroid hormone secretion, whereas high calcium levels in the blood prevent the release of parathyroid hormone.

What happens if I have too much parathyroid hormone?

A primary problem in the parathyroid glands, producing too much parathyroid hormone causes raised calcium levels in the blood (hypercalcaemia) and this is referred to as primary hyperparathyroidism. There is a similar but much rarer condition called tertiary hyperparathyroidism that causes hypercalcaemia due to excess parathyroid hormone production on the back drop of all four glands being overactive. Secondary hyperparathyroidism occurs in response to low blood calcium levels and is caused by other mechanisms, for example, kidney disease and vitamin D deficiency.

Mild primary hyperparathyroidism often causes few if any symptoms and is frequently diagnosed by finding a high calcium concentration on a routine blood test. Treatment may be by surgical removal of the affected gland(s) (parathyroidectomy). Further information on the symptoms for each condition can be found in the individual articles.

What happens if I have too little parathyroid hormone?

Too little parathyroid hormone or hypoparathyroidism, is a rare medical condition. It can result in low levels of calcium in the blood (hypocalcaemia). It is usually treated medically with oral calcium and vitamin D analogues but the availability of parathyroid hormone replacement therapy may change the approach to treatment for some patients.

What is peptide YY?

The full name for peptide YY is pancreatic peptide YY. It is a hormone that is secreted from endocrine cells called L-cells in the small intestine. There are two major forms of the peptide; one is 36 amino acids long (PYY1-36) and the other lacks the first two amino acids (PYY3-36). It is secreted alongside the hormone glucagon-like peptide 1. Peptide YY is released after eating, circulates in the blood and works by binding to receptors in the brain. Binding of peptide YY to brain receptors decreases appetite and makes people feel full after eating. Peptide YY also acts in the stomach and intestine to slow down the movement of food through the digestive tract.

How is peptide YY controlled?

Peptide YY secretion is mainly stimulated by the presence of food in the digestive tract, particularly fat and protein. The amount of peptide YY that is released into the blood depends on the amount of calories eaten, with higher calorie foods causing more peptide YY release than lower calorie foods. Peptide YY secretion can also be stimulated by digestive juices (such as bile) and another gastrointestinal hormone called cholecystokinin. The highest levels of peptide YY are found in the second hour after eating. Peptide YY levels then gradually decrease. Low levels of peptide YY are seen during long periods without eating, for example overnight.

What happens if I have too much peptide YY?

High peptide YY concentrations are unusual. They will cause a decrease in appetite and food intake. High peptide YY concentrations are associated with diseases where there is dramatic weight loss, such as anorexia nervosa, coeliac disease, inflammatory bowel disease (Crohn’s disease and ulcerative colitis) and some cancers.

What happens if I have too little peptide YY?

Low peptide YY concentrations are associated with an increase in appetite and food intake. Low peptide YY levels are seen in obesity and before the onset of type 2 diabetes and may contribute to weight gain in these conditions. However, low peptide YY concentrations are very unlikely to be the main cause of obesity as the levels decrease after weight gain has started. There has been some research into using peptide YY as a medication for obesity, aiming to decrease the appetite of people who are overweight. This research is still ongoing.

It is extremely rare to have a genetic (inherited) deficiency of peptide YY.

What is progesterone?

Progesterone belongs to a group of steroid hormones called progestogens. It is mainly secreted by the corpus luteum in the ovary during the second half of the menstrual cycle. It plays important roles in the menstrual cycle and in maintaining the early stages of pregnancy.

During the menstrual cycle, when an egg is released from the ovary at ovulation (approximately day 14), the remnants of the ovarian follicle that enclosed the developing egg form a structure called the corpus luteum. This releases progesterone and, to a lesser extent, oestradiol. The progesterone prepares the body for pregnancy in the event that the released egg is fertilised. If the egg is not fertilised, the corpus luteum breaks down, the production of progesterone falls and a new menstrual cycle begins.

If the egg is fertilised, progesterone stimulates the growth of blood vessels that supply the lining of the womb (endometrium) and stimulates glands in the endometrium to secrete nutrients that nourish the early embryo. Progesterone then prepares the tissue lining of the uterus to allow the fertilised egg to implant and helps to maintain the endometrium throughout pregnancy. During the early stages of pregnancy, progesterone is still produced by the corpus luteum and is essential for supporting the pregnancy and establishing the placenta. Once the placenta is established, it then takes over progesterone production at around week 8-12 of pregnancy. During pregnancy, progesterone plays an important role in the development of the foetus; stimulates the growth of maternal breast tissue; prevents lactation; and strengthens the pelvic wall muscles in preparation for labour. The level of progesterone in the body steadily rises throughout pregnancy until labour occurs and the baby is born.

Although the corpus luteum in the ovaries is the major site of progesterone production in humans, progesterone is also produced in smaller quantities by the ovaries themselves, the adrenal glands and, during pregnancy, the placenta.

How is progesterone controlled?

The formation of the corpus luteum (which produces the majority of progesterone) is triggered by a surge in luteinising hormone production by the anterior pituitary gland. This normally occurs at approximately day 14 of the menstrual cycle and it stimulates the release of an egg from the ovary and the formation of the corpus luteum. The corpus luteum then releases progesterone, which prepares the body for pregnancy. If the egg is not fertilised and no embryo is conceived, the corpus luteum breaks down and the production of progesterone decreases. As the lining of the womb is no longer maintained by progesterone from the corpus luteum, it breaks away and menstrual bleeding occurs, marking the start of a new menstrual cycle.

However, if the ovulated egg is fertilised and gives rise to an embryo, the cells that surround this early embryo (which are destined to form the placenta) will secrete human chorionic gonadotrophin. This hormone has a very similar chemical structure to luteinising hormone. This means it can bind to and activate the same receptors as luteinising hormone, meaning that the corpus luteum does not break down and instead keeps producing progesterone until the placenta is established.

What happens if I have too much progesterone?

There are no known serious medical consequences of having too much progesterone. Levels of progesterone do increase naturally in pregnancy as mentioned above.

High levels of progesterone are associated with the condition congenital adrenal hyperplasia. However, the high progesterone levels are a consequence of and not a cause of this condition. Also, high levels of progesterone are associated with an increased risk for developing breast cancer.

Progesterone, either alone or in combination with oestrogen, is taken by women as an oral contraceptive (‘the pill’). ‘The pill’ works by preventing ovulation, making it nearly 100% effective in preventing pregnancy.

Progesterone is used in hormone replacement therapy to relieve symptoms of the menopause in women. There are many recognised pros and cons to hormone replacement therapy – see the article on menopause for more information.

What happens if I have too little progesterone?

If progesterone is absent or levels are too low, irregular and heavy menstrual bleeding can occur. A drop in progesterone during pregnancy can result in a miscarriage and early labour. Mothers at risk of giving birth too soon can be given a synthetic form of progesterone to delay the onset of labour.

Lack of progesterone in the bloodstream can mean the ovary has failed to release an egg at ovulation, as can occur in women with polycystic ovary syndrome.

What is prolactin?

Prolactin is a hormone named originally after its function to promote milk production (lactation) in mammals in response to the suckling of young after birth. It has since been shown to have more than 300 functions in the body. These can be divided into a number of areas: reproductive, metabolic, regulation of fluids (osmoregulation), regulation of the immune system (immunoregulation) and behavioural functions.

In humans, prolactin is produced both in the front portion of the pituitary gland (anterior pituitary gland) and in a range of sites elsewhere in the body. Lactotroph cells in the pituitary gland produce prolactin, where it is stored and then released into the bloodstream. Human prolactin is also produced in the uterus, immune cells, brain, breasts, prostate, skin and adipose tissue.

How is prolactin controlled?

One of the main regulators of the production of prolactin from the pituitary gland is the hormone called dopamine, which is produced by the hypothalamus, the part of the brain directly above the pituitary gland. Dopamine restrains prolactin production, so the more dopamine there is, the less prolactin is released. Prolactin itself enhances the secretion of dopamine, so this creates a negative feedback loop.

Oestrogen is another key regulator of prolactin and has been shown to increase the production and secretion of prolactin from the pituitary gland. Studies have shown small increases in prolactin in the blood circulation of women during stages of their reproductive cycle where oestrogen levels are at their highest. This is also the case during and after pregnancy, which makes sense, since a higher level of circulating prolactin is needed to cause lactation to start.

In addition to dopamine and oestrogen, a whole range of other hormones can both increase and decrease the amount of prolactin released in the body, with some examples being thyrotropin-releasing hormone, oxytocin and anti-diuretic hormone.

What happens if I have too much prolactin?

The condition of having too much prolactin circulating in the blood is called hyperprolactinaemia. The most common causes of hyperprolactinaemia include pregnancy, medications that reduce dopamine action in the body, thyroid underactivity and benign pituitary tumours (known as prolactinomas). Symptoms can include the unwanted production of milk, disturbances to the menstrual cycle and symptoms due to oestrogen deficiency (in women) or testosterone deficiency (in men). The vast majority of patients with a prolactinoma can be treated successfully using drugs which mimic the action of dopamine. The most commonly used is cabergoline.

What happens if I have too little prolactin?

The condition of having too little prolactin circulating in the blood is called hypoprolactinaemia. This condition is very rare and may occur in people with pituitary underactivity.

A decrease in the amount of prolactin secreted can lead to insufficient milk being produced after giving birth. Most people with low prolactin levels do not have any specific medical problems, although preliminary evidence suggests they might have reduced immune responses to some infections.

What are prostaglandins?

Mechanism of action of the drug aspirin. Aspirin works by stopping prostaglandin being made: aspirin molecules (blue hexagons) enter the cell and chemically modify the cyclooxygenase enzyme (purple) to prevent prostaglandin being made.

Unlike most hormones, the prostaglandins are not secreted from a gland to be carried in the bloodstream and work on specific areas around the body. Instead, they are made by a chemical reaction at the site where they are needed and can be made in nearly all the organs in the body. Prostaglandins are part of the body’s way of dealing with injury and illness.

The prostaglandins act as signals to control several different processes depending on the part of the body in which they are made. Prostaglandins are made at sites of tissue damage or infection, where they cause inflammation, pain and fever as part of the healing process. When a blood vessel is injured, a prostaglandin called thromboxane stimulates the formation of a blood clot to try to heal the damage; it also causes the muscle in the blood vessel wall to contract (causing the blood vessel to narrow) to try to prevent blood loss. Another prostaglandin called prostacyclin has the opposite effect to thromboxane, reducing blood clotting and removing any clots that are no longer needed; it also causes the muscle in the blood vessel wall to relax, so that the vessel dilates. The opposing effects that thromboxane and prostacyclin have on the width of blood vessels can control the amount of blood flow and regulate response to injury and inflammation.

Prostaglandins are also involved in regulating the contraction and relaxation of the muscles in the gut and the airways.

Prostaglandins are known to regulate the female reproductive system, and are involved in the control of ovulation, the menstrual cycle and the induction of labour. Indeed, manufactured forms of prostaglandins – prostaglandin E2 and F2 can be used to induce (kick-start) labour.

How are prostaglandins controlled?

The chemical reaction that makes the prostaglandins involves several steps; the first step is carried out by an enzyme called cyclooxygenase. There are two main types of this enzyme: cyclooxygenase-1 and cyclooxygenase-2. When the body is functioning normally, baseline levels of prostaglandins are produced by the action of cyclooxygenase-1. When the body is injured (or inflammation occurs in any area of the body), cyclooxygenase-2 is activated and produces extra prostaglandins, which helps the body to respond to the injury.

Prostaglandins carry out their actions by acting on specific receptors; at least eight different prostaglandin receptors have been discovered. The presence of these receptors in different organs throughout the body allows the different actions of each prostaglandin to be carried out, depending on which receptor they interact with.

Prostaglandins are very short-lived and are broken down quickly by the body. They only carry out their actions in the immediate vicinity of where they are produced; this helps to regulate and limit their actions.

What happens if I have too much prostaglandins?

High levels of prostaglandins are produced in response to injury or infection and cause inflammation, which is associated with the symptoms of redness, swelling, pain and fever. This is an important part of the body’s normal healing process.

However, this natural response can sometimes lead to excess and chronic production of prostaglandins, which may contribute to several diseases by causing unwanted inflammation. This means that drugs, which specifically block cyclooxygenase-2, can be used to treat conditions such as arthritis, heavy menstrual bleeding and painful menstrual cramps and certain types of cancer, including colon and breast cancer. New discoveries are being made about cyclooxygenases which suggest that cyclooxygenase-2 is not just responsible for disease but has other functions.

Anti-inflammatory drugs, such as aspirin and ibuprofen, work by blocking the action of the cyclooxygenase enzymes and so reduce prostaglandin levels. This is how these drugs work to relieve the symptoms of inflammation. Aspirin also blocks the production of thromboxane and so can be used to prevent unwanted blood clotting in patients with heart disease.

What happens if I have too few prostaglandins?

Manufactured prostaglandins can be used to increase prostaglandin levels in the body under certain circumstances. For example, administration of prostaglandins can induce labour at the end of pregnancy or abortion in the case of an unwanted pregnancy. They can also be used to treat stomach ulcers, glaucoma and congenital-heart-disease’>congenital heart disease in newborn babies. Further advances in understanding how prostaglandins work may lead to newer treatments for a number of conditions.

What is relaxin?

In women, relaxin is secreted into the circulation by the corpus luteum in the ovary. During pregnancy it is also released from the placenta, the membranes which surround the fetus, and the lining of the uterus. In men, relaxin is secreted from the prostate gland and can be detected in the semen, but is not generally found in the blood circulation.

The effects of relaxin are most well-described during the female reproductive cycle and pregnancy. Relaxin levels in the circulation rise after ovulation, during the second half of the menstrual cycle. At this stage it is thought to relax the wall of the uterus by inhibiting contractions, and it also prepares the lining of the uterus for pregnancy. If pregnancy does not occur, relaxin levels drop again. During pregnancy, relaxin levels are at their highest in the first trimester. At this time it is believed to promote implantation of the developing fetus into the wall of the uterus and the growth of the placenta. Early in pregnancy, relaxin also inhibits contractions in the wall of the uterus, to prevent premature childbirth. Relaxin can regulate the mother’s cardiovascular and renal systems to help them adapt to the increase in demand for oxygen and nutrients for the fetus, and to process the resulting waste products. It is thought to do this by relaxing the mother’s blood vessels to increase blood flow to the placenta and kidneys.

Towards the end of pregnancy relaxin promotes rupture of the membranes surrounding the fetus and the growth, opening and softening of the cervix and vagina to aid the process of childbirth. There is also some evidence that relaxin can relax the ligaments at the front of the pelvis to ease delivery of the baby. There are several other factors involved in labour, but the exact trigger remains unclear.

The role of relaxin in men is less clear. However, there is evidence that it may increase the movement of sperm cells in the semen.

Relaxin belongs to the same family of hormones as insulin. Over the last decade, several relaxin-like peptides have been discovered, although the function of these peptides remains unclear.

Recent studies have revealed effects of relaxin on other systems in the body. Relaxin decreases tissue fibrosis in the kidney, heart, lungs and liver, and promotes wound healing. Tissue fibrosis is the formation of hard tissue as a result of inflammation which can lead to scarring and loss of organ function. This has made relaxin of interest to scientists studying how the heart heals after it has been damaged, which may help to treat heart failure in the future. In addition, relaxin can influence blood pressure by relaxing blood vessels; promote the growth of new blood vessels; and is also anti-inflammatory. All of these properties could make it a potential therapeutic target for the treatment of certain diseases.

How is relaxin controlled?

The control of relaxin release in humans is not fully understood. It is believed that relaxin production by the ovary during the menstrual cycle is stimulated by luteinising hormone from the pituitary gland, and that its release during pregnancy is also stimulated by human chorionic gonadotrophin from the placenta. It remains unclear whether relaxin can feed back to the pituitary or the fetus to affect luteinising hormone or human chorionic gonadotrophin levels and so control its own release.

Relaxin carries out its actions on the reproductive system and other organs by activating specific receptors on these tissues.

What happens if I have too much relaxin?

Disorders of relaxin secretion have not been described in detail. Studies have suggested that high levels of circulating relaxin in the mother are associated with premature birth, presumably via its effects on the rupture of the fetal membranes and the opening of the cervix. However, further research is needed to confirm these findings.

What happens if I have too little relaxin?

There is some evidence that low levels of relaxin may contribute to a condition known as scleroderma, where the skin thickens and hardens. This is caused by the development of fibrosis and scarring on the skin, which also occurs in the lung, stomach and blood vessels.

What is somatostatin?

Somatostatin is a hormone produced by many tissues in the body, principally in the nervous and digestive systems. It regulates a wide variety of physiological functions and inhibits the secretion of other hormones, the activity of the gastrointestinal tract and the rapid reproduction of normal and tumour cells. Somatostatin may also act as a neurotransmitter in the nervous system.

The hypothalamus is a region of the brain that regulates secretion of hormones from the pituitary gland located below it. Somatostatin from the hypothalamus inhibits the pituitary gland’s secretion of growth hormone and thyroid stimulating hormone.

In addition, somatostatin is produced in the pancreas and inhibits the secretion of other pancreatic hormones such as insulin and glucagon. Somatostatin is also produced in the gastrointestinal tract where it acts locally to reduce gastric secretion, gastrointestinal motility and to inhibit the secretion of gastrointestinal hormones, including gastrin and secretin.

Chemically altered equivalents of somatostatin are used as a medical therapy to control too much hormone secretion in patients with acromegaly and other endocrine conditions, and to treat some gastrointestinal diseases and a variety of tumours.

How is somatostatin controlled?

In the same way that somatostatin controls the production of several hormones, these hormones feed back to control the production of somatostatin. This is increased by raised levels of these other hormones and reduced by low levels.

Somatostatin is also secreted by the pancreas in response to many factors related to food intake, such as high blood levels of glucose and amino acids.

What happens if I have too much somatostatin?

Excessive somatostatin levels in the bloodstream may be caused by a rare endocrine tumour that produces somatostatin, called a ‘somatostatinoma’. Too much somatostatin results in extreme reduction in secretion of many endocrine hormones. An example of this is suppression of insulin secretion from the pancreas leading to raised blood glucose levels (diabetes). As somatostatin inhibits many functions of the gastrointestinal tract, its overproduction may also result in the formation of gallstones, intolerance to fat in the diet and diarrhoea.

What happens if I have too little somatostatin?

Since somatostatin regulates many physiological processes, too little somatostatin production would lead to a variety of problems, including too much secretion of growth hormone. However, there are very few reports of somatostatin deficiency.

What is testosterone?

Testosterone is produced by the gonads (by the Leydig cells in testes in men and by the ovaries in women), although small quantities are also produced by the adrenal glands in both sexes. It is an androgen, meaning that it stimulates the development of male characteristics.

Present in much greater levels in men than women, testosterone initiates the development of the male internal and external reproductive organs during foetal development and is essential for the production of sperm in adult life. This hormone also signals the body to make new blood cells, ensures that muscles and bones stay strong during and after puberty and enhances libido both in men and women. Testosterone is linked to many of the changes seen in boys during puberty (including an increase in height, body and pubic hair growth, enlargement of the penis, testes and prostate gland, and changes in sexual and aggressive behaviour). It also regulates the secretion of luteinising hormone and follicle stimulating hormone. To effect these changes, testosterone is often converted into another androgen called dihydrotestosterone.

In women, testosterone is produced by the ovaries and adrenal glands. The majority of testosterone produced in the ovary is converted to the principle female sex hormone, oestradiol.

How is testosterone controlled?

The regulation of testosterone production is tightly controlled to maintain normal levels in blood, although levels are usually highest in the morning and fall after that. The hypothalamus and the pituitary gland are important in controlling the amount of testosterone produced by the testes. In response to gonadotrophin-releasing hormone from the hypothalamus, the pituitary gland produces luteinising hormone which travels in the bloodstream to the gonads and stimulates the production and release of testosterone.

As blood levels of testosterone increase, this feeds back to suppress the production of gonadotrophin-releasing hormone from the hypothalamus which, in turn, suppresses production of luteinising hormone by the pituitary gland. Levels of testosterone begin to fall as a result, so negative feedback decreases and the hypothalamus resumes secretion of gonadotrophin-releasing hormone.

What happens if I have too much testosterone?

The effect excess testosterone has on the body depends on both age and sex. It is unlikely that adult men will develop a disorder in which they produce too much testosterone and it is often difficult to spot that an adult male has too much testosterone. More obviously, young children with too much testosterone may enter a false growth spurt and show signs of early puberty and young girls may experience abnormal changes to their genitalia. In both males and females, too much testosterone can lead to precocious puberty and result in infertility.

In women, high blood levels of testosterone may also be an indicator of polycystic ovary syndrome. Women with this condition may notice increased acne, body and facial hair (called hirsutism), balding at the front of the hairline, increased muscle bulk and a deepening voice.

There are also several conditions that cause the body to produce too much testosterone. These include androgen resistance, congenital adrenal hyperplasia and ovarian cancer.

The use of anabolic steroids (manufactured androgenic hormones) shuts down the release of luteinising hormone and follicle stimulating hormone secretion from the pituitary gland, which in turn decreases the amount of testosterone and sperm produced within the testes. In men, prolonged exposure to anabolic steroids results in infertility, a decreased sex drive, shrinking of the testes and breast development. Liver damage may result from its prolonged attempts to detoxify the anabolic steroids. Behavioural changes (such as increased irritability) may also be observed. Undesirable reactions also occur in women who take anabolic steroids regularly, as a high concentration of testosterone, either natural or manufactured, can cause masculinisation (virilisation) of women.

What happens if I have too little testosterone?

If testosterone deficiency occurs during fetal development, then male characteristics may not completely develop. If testosterone deficiency occurs during puberty, a boy’s growth may slow and no growth spurt will be seen. The child may have reduced development of pubic hair, growth of the penis and testes, and deepening of the voice. Around the time of puberty, boys with too little testosterone may also have less than normal strength and endurance, and their arms and legs may continue to grow out of proportion with the rest of their body.

In adult men, low testosterone may lead to a reduction in muscle bulk, loss of body hair and a wrinkled ‘parchment-like’ appearance of the skin. Testosterone levels in men decline naturally as they age. In the media, this is sometimes referred to as the male menopause (andropause).

Low testosterone levels can cause mood disturbances, increased body fat, loss of muscle tone, inadequate erections and poor sexual performance, osteoporosis, difficulty with concentration, memory loss and sleep difficulties. Current research suggests that this effect occurs in only a minority (about 2%) of ageing men. However, there is a lot of research currently in progress to find out more about the effects of testosterone in older men and also whether the use of testosterone replacement therapy would have any benefits.

What is thyroid stimulating hormone?

Thyroid stimulating hormone is produced and released into the bloodstream by the pituitary gland. It controls production of the thyroid hormones, thyroxine and triiodothyronine, by the thyroid gland by binding to receptors located on cells in the thyroid gland. Thyroxine and triiodothyronine are essential to maintaining the body’s metabolic rate, heart and digestive functions, muscle control, brain development and maintenance of bones.

How is thyroid stimulating hormone controlled?

When thyroid stimulating hormone binds to the receptor on the thyroid cells, this causes these cells to produce thyroxine and triiodothyronine and release them into the bloodstream. These hormones have a negative effect on the pituitary gland and stop the production of thyroid stimulating hormone if the levels of thyroxine and triiodothyronine are too high. They also switch off production of a hormone called thyrotropin-releasing hormone. This hormone is produced by the hypothalamus and it also stimulates the pituitary gland to make thyroid stimulating hormone.

What happens if I have too much thyroid stimulating hormone?

A simple blood test can measure thyroid stimulating hormone in the circulation. If a person has too much, this may indicate that their thyroid gland is not making enough thyroid hormone, that is, they have an underactive thyroid gland or hypothyroidism. People with an underactive thyroid often feel lethargic, experience weight gain and feel the cold. Their thyroid gland may enlarge to produce a goitre. Treatment is medication in the form of tablets to bring the level of thyroid hormones back to normal. This also reduces the amount of thyroid stimulating hormone in circulation. It is particularly important for pregnant women to have the correct amounts of thyroid stimulating hormone and thyroid hormones to ensure the healthy development of their babies. Thyroid stimulating hormone is one of the hormones measured in newborns. Rarely, problems from the pitutiary gland or rare genetic conditions can result in inappropriately high thyroid stimulating hormones, and high free thyroid hormone levels.

What happens if I have too little thyroid stimulating hormone?

If a person has too little thyroid stimulating hormone, it is most likely that their thyroid gland is making too much thyroid hormone, that is, they have an overactive thyroid or hyperthyroidism, which is suppressing the thyroid stimulating hormone. People with an overactive thyroid have the opposite symptoms to those with hypothyroidism, i.e. they lose weight (despite increasing the amount they eat), feel too hot and can experience palpitations or anxiety. They may also have a slightly enlarged thyroid gland. Treatment is medication in the form of tablets, which reduce the activity of the thyroid gland and return all thyroid hormone levels to normal. Rarely, problems in the pituitary gland can also result in a low thyroid stimulating hormone, and low free thyroid hormone levels.

What is thyrotropin-releasing hormone?

Thyrotropin-releasing hormone is one of the smallest hormones in the body, consisting of a miniature chain of just three amino acid building blocks. It is made by a cluster of nerve cells in the hypothalamus, an area at the base of the brain just above the pituitary gland. This nerve cell cluster is known as the paraventricular nucleus. The nerve fibres that come out of it carry the thyrotropin-releasing hormone and release it into the blood surrounding the pituitary gland, where it has its most important action. This is to regulate the formation and secretion of thyroid stimulating hormone in the pituitary gland, which in turn regulates the production of thyroid hormones in the thyroid gland. Thyrotropin-releasing hormone is very short-lived, lasting for a matter of two minutes and travelling less than an inch in the bloodstream to the pituitary gland before it is broken down.

Secretion of thyrotropin-releasing hormone by the hypothalamus can also stimulate the release of another hormone from the pituitary gland, prolactin. Apart from its role in control of thyroid stimulating hormone and prolactin release, thyrotropin-releasing hormone has a wider distribution in tissues of the nervous system where it may act as a neurotransmitter. For instance, an injection of thyrotropin-releasing hormone has effects on the arousal and feeding centres of the brain, causing wakefulness and loss of appetite.

How is thyrotropin-releasing hormone controlled?

As its name implies, the main effect of thyrotropin-releasing hormone is to stimulate the release of thyrotropin (also known as thyroid stimulating hormone) from the pituitary gland. Thyrotropin-releasing hormone is the master regulator of thyroid gland growth and function (including the secretion of the thyroid hormones thyroxine and triiodothyronine). These hormones control the body’s metabolic rate, heat generation, neuromuscular function and heart rate, among other things. If there is insufficient thyroid hormone available for the brain, this will be detected by the hypothalamus and thyrotropin-releasing hormone will be released into the blood supplying the pituitary gland. The effect of thyrotropin-releasing hormone on the pituitary gland is to trigger thyroid stimulating hormone release, which, in turn stimulates the thyroid gland to make more thyroid hormone. In summary, thyrotropin-releasing hormone is the brain’s first messenger signal in the many actions controlling thyroid hormone secretions.

Thyrotropin-releasing hormone (in its pharmaceutical formulation of ‘protirelin’) was widely used as a drug to test whether someone had thyroid overactivity. However, there are now more sensitive measurements that can detect very low levels of thyroid stimulating hormone in the blood. Thyrotropin-releasing hormone tests are still occasionally carried out but are normally used for the diagnosis of conditions caused by resistance to thyroid hormone action.

What happens if I have too much thyrotropin-releasing hormone?

There is no known case of too much thyrotropin-releasing hormone.

What happens if I have too little thyrotropin-releasing hormone?

If a person has too little thyrotropin-releasing hormone, they will develop thyroid underactivity (hypothyroidism). This is a rare condition, usually due to an injury or tumour which destroys this area of the hypothalamus. This situation is referred to as secondary or central hypothyroidism.

What is thyroxine?

Thyroxine is the main hormone secreted into the bloodstream by the thyroid gland. It is the inactive form and most of it is converted to an active form called triiodothyronine by organs such as the liver and kidneys. Thyroid hormones play vital roles in regulating the body’s metabolic rate, heart and digestive functions, muscle control, brain development and maintenance of bones.

How is thyroxine controlled?

The production and release of thyroid hormones, thyroxine and triiodothyronine, is controlled by a feedback loop system that involves the hypothalamus in the brain and the pituitary and thyroid glands. The hypothalamus secretes thyrotropin-releasing hormone which, in turn, stimulates the pituitary gland to produce thyroid stimulating hormone. This hormone stimulates the production of the thyroid hormones, thyroxine and triiodothyronine, by the thyroid gland.

This hormone production system is regulated by a feedback loop so that when the levels of the thyroid hormones (thyroxine and triiodothyronine) increase, they prevent the release of both thyrotropin-releasing hormone and thyroid stimulating hormone. This system allows the body to maintain a constant level of thyroid hormones in the body.

What happens if I have too much thyroxine?

The release of too much thyroxine in the bloodstream is known as thyrotoxicosis. This may be caused by overactivity of the thyroid gland (hyperthyroidism), as in Graves’ disease, inflammation of the thyroid or a benign tumour. Thyrotoxicosis can be recognised by a goitre, which is a swelling of the neck due to enlargement of the thyroid gland. Other symptoms of thyrotoxicosis include intolerance to heat, weight loss, increased appetite, increased bowel movements, irregular menstrual cycle, rapid or irregular heartbeat, palpitations, tiredness, irritability, tremor, hair thinning/loss and retraction of the eyelids resulting in a ‘staring’ appearance.

What happens if I have too little thyroxine?

Too little production of thyroxine by the thyroid gland is known as hypothyroidism. It may be caused by autoimmune diseases, poor iodine intake or caused by the use of certain drugs. Sometimes, the cause is unknown. Thyroid hormones are essential for physical and mental development so untreated hypothyroidism before birth or during childhood can cause mental impairment and reduced growth.

Hypothyroidism in adults causes reduced metabolism. It can result in symptoms such as fatigue, intolerance of cold temperatures, low heart rate, weight gain, reduced appetite, poor memory, depression, stiffness of the muscles and reduced fertility. See the article on hypothyroidism for more information.

What is triiodothyronine?

Triiodothyronine is the active form of the thyroid hormone, thyroxine. Approximately 20% of triiodothyronine is secreted into the bloodstream directly by the thyroid gland. The remaining 80% is produced from conversion of thyroxine by organs such as the liver and kidneys. Thyroid hormones play vital roles in regulating the body’s metabolic rate, heart and digestive functions, muscle control, brain development and function, and the maintenance of bones.

How is triiodothyronine controlled?

The production and release of thyroid hormones, thyroxine and triiodothyronine, is controlled by a feedback loop involving the hypothalamus, pituitary gland and thyroid gland. Activation of thyroid hormones is then controlled in body tissues such as the liver, brain and kidneys by enzymes called deiodinases which convert thyroxine into the active form triiodothyronine. Most of the body’s circulating triiodothyronine (about 80%) is produced in this way.

The thyroid hormone production system is regulated by a feedback loop so that when the levels of the thyroid hormones thyroxine and triiodothyronine increase, they prevent the release of both thyrotropin-releasing hormone from the hypothalamus and thyroid stimulating hormone from the pituitary gland. This system allows the body to maintain a constant level of thyroid hormones in the body.

What happens if I have too much triiodothyronine?

Thyrotoxicosis is the name of the condition in which people have too much thyroid hormone in their bloodstreams. It may result from overactivity of the thyroid gland (hyperthyroidism) from conditions such as Graves’ disease, inflammation of the thyroid or a benign tumour. Thyrotoxicosis may be recognised by a goitre, which is a swelling of the neck due to enlargement of the thyroid. Other symptoms of thyrotoxicosis include heat intolerance, weight loss, increased appetite, increased bowel movements, irregular menstrual cycle, rapid or irregular heartbeat, palpitations, tiredness, irritability, tremor, hair thinning/loss and retraction of the eyelids, which results in a ‘staring’ appearance.

What happens if I have too little triiodothyronine?

Hypothyroidism is the term for the production of too little thyroid hormone by the thyroid gland. This may be because of autoimmune diseases (such as Hashimoto’s disease), very poor iodine intake or due to some medications. Since thyroid hormones are essential for physical and mental development, untreated hypothyroidism before birth and during childhood can result in learning disability and reduced growth.

Hypothyroidism in adults results in a slowing of the body’s functions with symptoms such as tiredness, intolerance to cold temperatures, low heart rate, weight gain, reduced appetite, poor memory, depression, stiffness of the muscles and reduced fertility. See the article on hypothyroidism for more information.

What is vitamin D?

Vitamin D is actually a hormone rather than a vitamin; it is required to absorb calcium from the gut into the bloodstream. Vitamin D is mostly produced in the skin in response to sunlight and is also absorbed from food eaten (about 10% of vitamin D is absorbed this way) as part of a healthy balanced diet. The liver and kidneys convert vitamin D (produced in the skin and taken up in the diet), into the active hormone, which is called calcitriol. Active vitamin D helps to increase the amount of calcium the gut can absorb from eaten food into the bloodstream and also prevents calcium loss from the kidneys. Vitamin D modifies the activity of bone cells and is important for the formation of new bone in children and adults.

How is vitamin D controlled?

A fall in the concentration of calcium in the bloodstream is detected by the parathyroid glands, which then produce parathyroid hormone. Parathyroid hormone increases the activity of the enzyme (catalyst) that produces active vitamin D. This increase in the concentration of calcium together with vitamin D feeds back to the parathyroid glands to stop further parathyroid hormone release. The production of vitamin D is also directly regulated by calcium, phosphate and calcitriol.

What happens if I have too little vitamin D?

Vitamin D deficiency is common in the UK, probably due to lifestyle changes and lack of sun exposure. If you have severely low vitamin D levels you are unable to maintain an adequate concentration of calcium in your blood for bone growth. This causes rickets in children and osteomalacia in adults. As the role of vitamin D as a regulator of other functions throughout the body has emerged, it has been suggested that a lack of vitamin D is linked to an inability to fight infections effectively, muscle weakness, fatigue and the development of diabetes, certain cancers, multiple sclerosis, depression, heart disease, high blood pressure, and stroke, although the direct relevance and mechanisms underlying these responses remain unknown.

Oily fish such as sardines, mackerel and salmon are good dietary sources of vitamin D. Calcium can be found in cow’s milk and dairy products. In the UK, foods such as breakfast cereals and margarine are fortified with vitamin D. Adequate exposure to sunlight is important, especially between April and October, for around 15 minutes daily. Public Health England recommends vitamin D supplements are taken by people in at risk groups (for example, women who are pregnant or breast-feeding, young children and those with osteoporosis).

What happens if I have too much vitamin D?

It is very rare to have too much vitamin D. If you have too much vitamin D the level of calcium in your blood may increase and this causes a condition known as hypercalcaemia, which can cause a number of symptoms such as nausea, vomiting, constipation, tiredness, confusion, depression, headaches, muscle weakness, the need to pass urine more frequently and feeling thirsty. However, this condition is very rare.

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