Women's Health Series // Hormone Basics
I have decided to start writing a series of blogposts that will be focusing on women's health, specifically how our hormones function and influence many aspects of our health and wellbeing. I have SO many ideas of posts that I would like to write, mostly thanks to all of the questions that I have been asked by you as readers, however I didn't think I could really dive into things without first covering the basics of female hormones today and then the menstrual and ovarian cycles next week. The idea behind these two posts is to have them available here on the blog to refer back to in future posts, where understanding the function of different reproductive hormones will aid in your understanding of each topic as a whole. I really struggled with figuring out how to compile this post, but will have hopefully done it some justice nevertheless. Before we get started, I thought I would walk you through how I have formatted things in this post. Each section will be structured as follows:
What is it?
Where is it produced?
Where and how does it act? What does it do?
How are its levels controlled?
What happens when levels are too low?
What happens when levels are too high?
In this post I will be addressing the role of these hormones in women, so bear in mind that they all have similar but different effects and will be regulated slightly differently in men. I will also likely come back and add more information to this post in future as I learn more about these amazing, complex hormones and systems. Ready to dive in? Let's go!
There are three forms of oestrogen – oestrone, oestradiol and oestriol – that are largely responsible for secondary sexual characteristics in women. Males also produce and need oestrogen, but in much smaller amounts than females.
Oestrogens are produced primarily by the ovaries. Smaller amounts are produced by adrenal glands, breasts, fat cells, as well as the placenta during pregnancy. After being produced in the ovaries, oestrogen is transported to other areas of the body via the bloodstream. When the hormone gets to its target cell, oestrogen crosses the cell membrane, is picked up by a carrier protein, and is then transported to the cell nucleus (this is where our DNA is housed). Oestrogen then works by binding to certain genes to change their expression, which ultimately changes what that target cell does.
In women, oestrogen assists in endometrial regrowth, ovary development, and ovulation, as well as the secondary sexual characteristics including breast development (influences fat deposition in breast tissue), widening of the hips, fat deposition primarily on the thighs and hips, and a shorter period necessary for bone maturation. Non-reproductive roles of oestrogen include positive effects on cholesterol levels (lowers LDL, increases HDL) and thus heart health, as well as positive effects on bone health through the promotion of calcium absorption and slowing down of bone breakdown.
In women, levels are regulated by interactions between the brain and the ovaries via the Hypothalamic-Pituitary-Ovarian (HPO) Axis.
(if you're already feeling a bit tired from reading through all of this information, I have included this awesome video from Khan Academy, which goes into most of the details about oestrogen that I have discussed)
What is it? Oestradiol is a form of oestrogen found in the body.
Where is it produced? Oestradiol is produced primarily in the ovaries. During pregnancy the placenta is also involved in producting oestradiol.
What does it do? Oestradiol (along with progesterone) is responsible for preparing the body for pregnancy and regulating the menstrual cycle. It promotes the thickening of the endometrial lining prior to ovulation so that an egg can implant in the uterine wall if it becomes fertilised. It is also responsible for the secondary sex characteristics in females along with other forms of oestrogen.
How are its levels controlled? Oestradiol production is controlled by hormones involved in the HPO Axis. FSH and LH are released to stimulate follicle development in the ovaries. As a follicle develops, theca and granulosa cells inside of it team up to produce and release oestradiol into the bloodstream. Following ovulation the follicle remnants become a corpus luteum, which produces both progesterone and oestradiol. Oestradiol levels are at their highest when ovulation takes place, and at their lowest during menstruation (when an egg is not fertilised and the endometrial lining needs to be shed). Oestradiol levels fall naturally during menopause due to the depletion of follicles.
What happens when levels are too low? Oestradiol plays an important role in bone development, so low levels of oestradiol can contribute to inadequate bone growth and osteoporosis in the long-term. In young girls, low levels of oestradiol can result in delayed breast development, a disrupted or absent period, and infertility.
What happens when levels are too high? In females, elevated levels of oestradiol can result in mild (acne, constipation, low libido, depression) or more severe effects (infertility, stroke, heart attack, unexplained weight gain, and an increased risk of developing uterine and breast cancer).
What is it? Oestriol is another form of oestrogen found in the body. During pregnancy oestriol levels are often used as an indicator of foetal and placental health.
Where is it produced? During pregnancy, oestriol is produced by the placenta from a compound that is produced by the foetus. Foetal adrenal glands synthesise a hormone called dehydroepiandrosterone sulphate (DHEAS), which is converted in the liver of the foetus, transported to the placenta, and is finally converted into oestriol.
What does it do? For most of pregnancy, the majority of oestriol produced is bound to other chemicals and thus prevents oestriol from exerting any biological effects. Oestriol does, however, promote the growth of the uterus during pregnancy, increases its sensitivity to other pregnancy-related hormones, and helps prepare the uterus for birth.
How are its levels controlled? Oestriol levels begin to increase from week eight of pregnancy onwards. There is research to suggest that labour may be triggered when oestriol becomes the dominant hormone.
What happens when levels are too low? Oestriol levels are naturally low in non-pregnant women. During pregnancy, low levels of unbound oestriol can indicate that there are problems with the baby and/or the placenta. In the later stages of pregnancy, low oestriol levels may indicate that labour may not occur spontaneously and may need to be induced.
What happens when levels are too high? Increased levels of oestriol, or rather a sudden surge in oestriol, will usually take place around three weeks before labour begins.
What is it? Oestrone is the final of three forms of oestrogen made by the body. It is one of the major oestrogens present in postmenopausal women.
Where is it produced? It is thought that around 50% of oestrone is primarily synthesised by the ovaries, whilst the remaining 50% is produced by adipose tissue and the adrenal glands.
What does it do? Oestrone is less active than oestradiol, so it is thought that oestrone may act as a reservoir that is converted into oestradiol as needed.
What happens when levels are too low? Low levels of oestrone can cause osteoporosis, fatigue, hot flushes, low libido, and depression.
What happens when levels are too high? Overproduction of oestrone may be associated with development of breast and endometrial cancer in women. However aside from these effects, the full extent of how high oestrone levels affect the body are largely unknown.
What is it? Progesterone also belongs to the group of steroid hormones.
Where is it produced? Progesterone is mainly produced and secreted by the corpus luteum (the remnants of the ovarian follicle following ovulation) in the ovary during the second half of a menstrual cycle. If an egg is fertilised and pregnancy is established, the corpus luteum is still responsible for producing the majority of progesterone until around week 8-12 when the placenta is able to take over progesterone production. Progesterone is produced in smaller amounts by the ovaries and adrenal glands.
Where and how does it act? What does it do? Progesterone plays an important role in regulating the menstrual cycle as it assists in endometrial regrowth and inhibits FSH and LH release. It is also important for preparing the body for pregnancy in case a released egg is fertilised. It does this through stimulating the growth of blood vessels that supply the lining of the uterus, and stimulates glands in the endometrial lining to secrete nutrients that will nourish a growing embryo. Once pregnancy is established, progesterone plays an important role in the development of a growing foetus, stimulates the growth of maternal breast tissue, prevents lactation prior to birth, and helps to strengthen the pelvic floor in preparation for labour.
How are its levels controlled? Progesterone levels depend primarily on the stage of the menstrual cycle as the hormone is primarily secreted by the corpus luteum following ovulation. If an egg is not fertilised following ovulation, the corpus luteum breaks down, progesterone secretion declines, and a new cycle begins. If an egg is fertilised, the corpus luteum continues to secrete progesterone until the placenta is established, following which progesterone levels increase steadily throughout pregnancy until a baby is born.
What happens when levels are too low? Low levels of progesterone can result in irregular and/or heavy menstrual bleeding. It can often indicate that an ovary has failed to release an egg when ovulation should have taken place, as can occur in women with PCOS. In pregnant women, a drop in progesterone levels can result in miscarriage or early labour.
What happens when levels are too high? There are no known serious consequences of increased progesterone levels, however high levels of the hormone may be associated with increased breast cancer risk.
What is it? Testosterone is a sex hormone that is responsible for many male-specific physical characteristics, and plays an important role in reproduction and the maintenance of bone and muscle strength.
Where is it produced? In women, testosterone is primarily produced by the ovaries, with smaller amounts produced by the adrenal glands. In women, the majority of testosterone produced in the ovary is converted to oestradiol.
Where and how does it act? What does it do? Testosterone is produced in far greater levels in men than women, and it stimulates the development of male-specific physical characteristics such as the male internal and external reproductive organs as well as the production of sperm in adult life. Testosterone also plays a role in signalling the body to produce new blood cells, promotes muscle and bone strength during and after puberty, and enhances libido in both men and women.
What happens when levels are too high? In both males and females, too much testosterone can lead to early puberty and may result in infertility. High blood levels of testosterone may be an indicator of PCOS in women, who may notice signs such as menstrual irregularities, increased acne, body and facial hair (hirsutism) balding at the front of the hairline, and other ‘male’ characteristics.
Cortisol isn't a reproductive hormone, but I thought it would be worthwhile including it in this blog post as it's a really important one that is impacted by stress, activity, and other things, and in turn can influence the menstrual cycle and reproductive health.
What is it? Cortisol is a steroid hormone that regulates many bodily processes, including metabolism and the immune response. It also has a very important role in helping the body respond to stress.
Where is it produced? Cortisol is made in the cortex of the adrenal glands. It is released into the bloodstream, and is transported throughout the body.
Where and how does it act? What does it do? There are receptors for cortisol on almost every cell in the body, thus cortisol can have many different effects depending on the cells it acts upon. Some of the main effects of cortisol include the control of blood sugar levels, regulation of metabolism, anti-inflammatory effects, memory formation, controlling salt and water balance, influencing blood pressure, and helping with foetal development. Cortisol is also secreted in response to stress.
How are its levels controlled? Levels of cortisol follow a diurnal rhythm. They are generally high in the morning when we wake up and then fall throughout the day, however this pattern can be disrupted in night-shift workers and when our sleep patterns are disturbed. The secretion of cortisol is mainly controlled by the Hypothalamic-pituitary-adrenal (HPA) Axis. When cortisol levels are low, a group of cells in the hypothalamus releases corticotrophin-releasing hormone, which signals the pituitary gland to secrete adrenocorticotropic hormone into the bloodstream. High levels of adrenocorticotropic hormone are detected by the adrenal glands, which secrete cortisol. As cortisol levels rise, they block the release of corticotrophin-releasing hormone from the hypothalamus and adrenocorticotrophic hormone from the pituitary, which subsequently leads to a drop in cortisol levels.
What happens when levels are too low? Very low levels of cortisol can be due to a condition called Addison's disease.
What happens when levels are too high? High cortisol levels over a prolonged time can result in reduced sex drive and amenorrhoea (irregular/infrequent or cessation of periods). In extreme cases chronically elevated cortisol levels can lead to Cushing's syndrome, which is characterised by symptoms such as rapid weight gain in the face, chest, and abdomen, high blood pressure, osteoporosis, skin changes, muscle weakness, mood swings, and increased thirst and frequency of urination.
Gonadotropin-releasing hormone (GnRH)
What is it? GnRH is a hormone that is responsible for controlling the production of LH and FSH from the pituitary gland.
Where is it produced? GnRH is produced and secreted by specialised nerve cells in the hypothalamus and is released into tiny blood vessels that carry it straight to the pituitary gland.
Where and how does it act? What does it do? GnRH acts on the anterior pituitary gland, where it stimulates the production of FSH and LH.
How are its levels controlled? The production of GnRH in women is controlled by the levels of oestrogens and progesterone. If oestrogen levels increase, GnRH production decreases (and vice versa). The only exception to this is when ovulation occurs at the midpoint of a woman's menstrual cycle where a dominant follicle produces very high levels of oestradiol, which stimulates a large increase in GnRH secretion, which stimulates a LH surge, and subsequently triggers the release of a mature egg.
What happens when levels are too low? Trauma or damage to the hypothalamus can also cause a loss of GnRH secretion, which will stop the normal production of FSH and LH. This can result in amenorrhoea as well as loss of production of hormones from the ovaries in women.
What happens when levels are too high? The effects are of having too much GnRH are not well understood. In very rare cases, pituitary tumours can develop, which increase production of gonadotrophins and may lead to overproduction of testosterone or oestrogen.
Both FSH and LH are gonadotrophic hormones that are produced and released by the anterior pituitary gland, and are transported in the blood stream to the ovaries in women. FSH and LH control the levels of hormones produced by the ovaries and are important in controlling ovulation.
Follicle stimulating hormone (FSH)
What is it? FSH (like LH) is a gonadotrophic hormone that stimulates development of egg cells within structures called follicles.
Where is it produced? FSH is produced and released by the anterior pituitary gland into the bloodstream.
Where and how does it act? What does it do? In women, FSH is important for the development and function of ovaries. It travels to the ovaries along with LH, where it binds to receptors and stimulates the growth of ovarian follicles. FSH also influences oestradiol production.
How are its levels controlled? FSH production and secretion is regulated by the HPO Axis. As hormone levels fall towards the end of a menstrual cycle in women, nerve cells in the hypothalamus are stimulated to produce and release more GnRH. GnRH stimulates the anterior pituitary gland to produce and secrete more FSH, which travels to the ovaries to stimulate the growth of follicles. The increasing amounts of oestradiol and inhibin, which are produced and secreted by cells found inside of growing follicles, is sensed by the hypothalamus and pituitary gland. This results in less GnRH and FSH being released. Oestradiol continues to increase steadily up until a point where it triggers a surge in both LH and FSH, which stimulates ovulation. Following ovulation the levels of FSH and LH decrease as their release is inhibited by high levels of progesterone secreted by the corpus luteum. In the case of an unfertilised egg, the corpus luteum breaks down, progesterone production decreases, and this cycle begins again.
What happens when levels are too low? A lack of FSH can result in incomplete development during puberty and poor ovarian function. This can lead to infertility due to the fact that ovarian follicles will not grow properly and release an egg without the action of adequate FSH.
What happens when levels are too high? High levels of FSH can indicate problems with ovarian function. If the ovaries fail to produce enough oestrogen and/or inhibin, feedback control of FSH and LH production will not function as it should. In this case, the levels of both hormones will rise and may result in primary ovarian failure. In women, FSH levels do rise naturally during menopause and reflect a change in ovarian function as well as a decline in both oestrogen and progesterone production. There are rare cases of pituitary conditions that can result in increased levels of FSH in the bloodstream, hyperstimulation and enlarging of the ovaries, and pelvic pain due to the accumulation of fluid in the abdomen.
Luteinising hormone (LH)
What is it? LH (like FSH) is a gonadotrophic hormone that is crucial for regulating the proper function of ovaries in women.
Where is it produced? LH is produced and released by the anterior pituitary gland into the bloodstream.
Where and how does it act? What does it do? In women, LH plays different roles throughout the course of a menstrual cycle. During the first two weeks of a cycle, LH stimulates follicles in the ovary to develop, and produce and secrete oestradiol. A surge in LH is responsible for the release of a mature oocyte (egg) from a mature ovarian follicle. Following the release of an egg, LH stimulates the corpus luteum to produce progesterone.
How are its levels controlled? The production and secretion of LH (like FSH) is regulated by the HPO Axis. As LH levels fall towards the end of a menstrual cycle, nerve cells in the hypothalamus are stimulated to produce and release GnRH. GnRH stimulates the anterior pituitary gland to produce and secrete more LH, which is carried to the ovaries where it regulates hormone secretions and the development of ova. Increasing levels of oestradiol and inhibin during follicle development suppresses the release of GnRH from the hypothalamus and subsequently LH from the pituitary gland. Once again, the surge in both LH and FSH that takes place at the midpoint of the menstrual cycle stimulates ovulation, following which their levels decrease until a breakdown in the corpus luteum takes place.
What happens when levels are too low? Low levels of LH will affect fertility as this hormone is required to support normal ovarian function. Low levels of LH mean that ovulation may not occur and menstrual periods might not occur regularly. An example of a condition which can be caused by too little luteinising hormone is amenorrhoea.
What happens when levels are too high? High levels of LH in the bloodstream can indicate decreased hormone production from the ovaries, and thus too much LH in the blood stream can be an indicator of infertility. In PCOS, an imbalance between LH and FSH can stimulate an inappropriate production of testosterone and result in reduced fertility.
Human chorionic gonadotropin (hCG)
What is it? Human chorionic gonadotrophin (hCG) is a reproductive hormone that is essential for establishing and maintaining early pregnancy.
Where is it produced? hCG is produced by the cells that surround a growing embryo following fertilisation that eventually go on to form the placenta.
Where and how does it act? What does it do? Following ovulation, the corpus luteum produces progesterone until an egg is either fertilised or not. If an egg is not fertilised, menstruation occurs. However if an egg is fertilised, it is important that progesterone levels remain elevated to allow the embryo to implant in the endometrial lining. hCG is the embryonic hormone that ensures that the corpus luteum continues to produce sufficient progesterone during the first trimester of pregnancy. hCG also may play a role in ensuring that the endometrium is ready to receive an implanting embryo. Once the placenta is established (around week 12 of pregnancy), it becomes the primary producer of progesterone and hCG is no longer required to maintain the pregnancy. However hCG may still have additional roles throughout the course of pregnancy
How are its levels controlled? hCG is produced by trophoblast cells that surround a developing embryo around 5 days after fertilisation. Levels of the hormone double every 2-3 days as the embryo and placenta develop, can be detected in the urine from 7-9 days after fertilisation, and levels peak at around 6 weeks of pregnancy.
What happens when levels are too low? Low levels of hCG can indicate a failing pregnancy, and are often observed in ectopic pregnancies (where the embryo implants outside of the uterus) or in the case of miscarriages.
What happens when levels are too high? There is no strong evidence to show that high hCG levels have negative consequences, however elevated levels of hCG in the blood or urine can serve as a tumour marker in rare cases.
What is the HPO Axis?
The hypothalamic-pituitary-gonadal (HPG) axis involves interaction between the hypothalamus, pituitary gland and the gonads (ovaries in females). It is also known as the hypothalamic-pituitary-ovarian (HPO) axis in women. The regulation of these interactions relies upon complex negative feedback loops:
The hypothalamus secretes GnRH, which travels down and binds to receptors in the pituitary gland
This causes the release of LH and FSH, which travel in the bloodstream to the ovaries
LH and FSH bind to the ovaries and stimulate the maturation of ovarian follicles, which results in the production of oestrogen and inhibin
Increased levels of oestrogen and inhibin cause negative feedback on the pituitary gland and hypothalamus, which leads to decreased production of GnRH, LH, and FSH
This in turn results in decreased production of oestrogen and inhibin
What is it? Prolactin is a hormone that is primarily responsible for milk production (lactation), as well as a number of other functions in the body.
Where is it produced? Prolactin is produced in the anterior pituitary gland as well as a number of sites elsewhere in the body (uterus, immune cells, brain, breasts, skin, and adipose tissue).
Where and how does it act? What does it do? Prolactin stimulates the mammary glands to produce milk (lactation) following pregnancy. During pregnancy, increased levels of prolactin stimulate enlargement of the mammary glands to prepare for milk production. The hormone also plays an important role in maternal behaviour. In addition to its role in lactation, prolactin also regulates reproductive function, influences behaviour, and is involved in both osmoregulation and immunoregulation. In fact, prolactin has over 300 known roles in the body.
How are its levels controlled? Dopamine (a hormone produced by the hypothalamus) is one of the main regulators of prolactin production and secretion. High levels of dopamine suppress the production and release of prolactin, and vice versa. Oestrogen also plays a role in regulating prolactin production and secretion. Research has found that prolactin levels increase slightly during the stages of the menstrual cycle where oestrogen is at its highest. In addition to these, a range of other hormones including oxytocin, anti-diuretic hormone (ADH), and thyortopin-releasing hormone can influence prolactin levels in the body.
What happens when levels are too low? Low prolactin secretion can lead to insufficient milk production after giving birth.
What happens when levels are too high? Having high levels of prolactin circulation is known as hyperprolactinaemia. This is most commonly caused by pregnancy, medications that reduce dopamine action in the body, thyroid underactivity, and the presence of benign pituitary tumours. High prolactin levels can result in the unwanted production of milk, menstrual cycle disturbances, and oestrogen deficiency symptoms.
What is it? Relaxin is a hormone produced by the ovaries and placenta. It relaxes the ligaments in the pelvis and softens and widens the cervix in preparation for childbirth.
Where is it produced? Following fertilisation of an egg, relaxin is secreted by the corpus luteum in the ovary. During pregnancy it is also released by the placenta, the membranes that surround the foetus, and the endometrial lining.
Where and how does it act? What does it do? During the second half of the menstrual cycle, relaxin acts on the wall of the uterus by inhibiting contractions and helps to prepare the lining of the uterus for pregnancy. During the early part of pregnancy it is believed that relaxin promotes implantation of the developing foetus into the uterine lining as well as the growth of the placenta. Relaxin also plays a role in regulating a mother's cardiovascular and renal systems as she adapts to the increased demand to oxygen and nutrients for the foetus, as well as processing and excretion of foetal waste products. It is thought that relaxin does this by relaxing the mother's blood vessels to allow for increased blood flow to the placenta and kidneys. At the end of pregnancy, relaxin promotes the rupture of the membranes surrounding the foetus as well as the growth, opening, and softening of the cervix and vagina in preparation for childbirth.
How are its levels controlled? Relaxin levels rise after ovulation during the second half of the menstrual cycle, and drop again if an egg is not fertilised and pregnancy does not occur. The control of relaxin production and release isn't fully understood, however it is believed that relaxin production by the ovary during the menstrual cycle is stimulated by LH and during pregnancy is also stimulated by hCG from the placenta.
What happens when levels are too low? There is some evidence that low levels of relaxin may contribute to a condition where the skin thickens and hardens (scleroderma).
What happens when levels are too high? High levels of circulating relaxin may be associated with premature birth via its effects on the opening of the cervix and rupture of foetal membranes, however further research is needed to support preliminary evidence of this.
What is it? Inhibin is a hormone that inhibits FSH production.
Where is it produced? In women, inhibin is produced in the ovaries, pituitary gland, placenta, corpus luteum, and other organs.
Where and how does it act? What does it do? How are its levels controlled? FSH stimulates the secretion of inhibin from granulosa cells found in ovarian follicles. Inhibin, in turn, suppresses FSH. The secretion of FSH is diminished by GnRH, and is enhanced by insulin-like growth factor-1 (IGF-1).
What is it? Oxytocin acts on organs such as the breast and uterus, and acts as a chemical messenger in the brain that controls key aspects of the reproductive system (childbirth and lactation) as well as aspects of human behaviour.
Where is it produced? Oxytocin is produced by the hypothalamus and is secreted into the bloodstream by the posterior pituitary gland.
Where and how does it act? What does it do? Oxytocin has two main actions in the body, namely the contraction of the uterus during childbirth and lactation. During labour, oxytocin stimulates the contraction of uterine muscles and also increases prostaglandin production, which helps increase contractions even further. During breastfeeding, oxytocin promotes movement of milk into the breast. Oxytocin has also been suggested to play an important role in social behaviour. The hormone is known to be important in sexual arousal, recognition, trust, anxiety, and mother-infant bonding.
How are its levels controlled? Oxytocin is controlled by a positive feedback loop, namely the release of the hormone causes an action that stimulates further release. When uterine contractions start at the beginning of labour, oxytocin is released. This oxytocin acts on the uterus to stimulate more contractions, which in turns stimulates the release of more oxytocin. This is why during labour, contractions should increase in intensity and frequency until the baby is delivered. Similarly, positive feedback of oxytocin is involved in the milk-ejection reflex. When a baby sucks on its mother's breast, oxytocin is secreted into the bloodstream, which promotes the movement of milk into the breast and action of oxytocin on the brain to stimulate further oxytocin. This feedback continues until the baby stops feeding.
Anti-Müllerian hormone (AMH)
What is it? AMH is a hormone released by ovarian follicles in women, and is thus a good indicator of the number of eggs that a woman has (ovarian reserve). AMH levels are routinely used to predict how well a woman is likely to respond to ovarian stimulation for in vitro fertilisation (IVF) treatment.
How are its levels controlled? In women, levels of AMH peak around puberty and remain relatively constant until after menopause (when no ovarian follicles remain).
What happens when levels are too low? AMH levels are usually low following the menopause. Some studies suggest that AMH levels may be lower than normal in women who experience premature ovarian failure, however AMH levels need to be interpreted with care due to the fact that you cannot derive conclusions from looking at just AMH in isolation.
What happens when levels are too high? High levels of AMH can indicate PCOS, however this must also be interpreted within the context of other hormone levels and diagnostic criteria.
What is it? Thyrotropin-releasing hormone is a very small hormone comprised of only three amino acids that plays an important role in regulating the production of hormones by the thyroid gland.
Where is it produced? Thyrotropin-releasing hormone is produced by the paraventricular nucleus (a cluster of cells in the hypothalamus). After being produced, nerve fibres exiting the hypothalamus carry the hormone through the bloodstream to the pituitary gland. It has a very short life-span, lasting only ±2 minutes before it is broken down (hence the need to be produced near to its site of action).
Where and how does it act? What does it do? The main effect of thyrotropin-releasing hormone is to regulate the formation and secretion of thyroid stimulating hormone (TSH) in the pituitary gland, which is responsible for regulating hormone production in the thyroid gland. It is thus the master regulator of thyroid gland growth and function, mostly through the production and secretion of thyroid hormones, which control the body's metabolic rate, thermoregulation, neuromuscular function, heart rate, and a number of other functions. Interestingly enough, thyrotropin-releasing hormone release by the hypothalamus can also stimulate the release of prolactin from the pituitary gland. The hormone can also act as a neurotransmitter throughout the nervous system, and has known effects on the arousal and feeding centres of the brain (thus affecting wakefulness and appetite).
How are its levels controlled? When the hypothalamus detects low levels of thyroid hormones, it releases thyrotropin-releasing hormone into the bloodstream that travels straight to the pituitary gland. Here the hormone triggers the release of TSH, which stimulates the thyroid to produce more thyroid hormones. Thyrotropin-releasing hormone is thus the first chemical messenger in a series of actions that control thyroid hormone secretion.
What happens when levels are too low? Low levels of thyrotropin-releasing hormone will occur most often as a result of an injury or tumour which destroys the area of the hypothalamus where the hormone is produced. This is known as secondary or central hypothyroidism, and ultimately results in the development of thyroid underactivity.
Thyroid stimulating hormone (TSH)
What is it? TSH is a hormone that plays an important role in regulating the production of thyroid hormones by the thyroid gland.
Where is it produced? After stimulation by the action of thyrotropin-releasing hormone, TSH is produced and released into the bloodstream by the pituitary gland.
Where and how does it act? What does it do? TSH controls the production of thyroid hormones (thyroxine and triiodothyronine) by the thyroid gland. These hormones are essential to maintenance of the body's metabolic rate, heart and digestive functions, muscle control, brain development, and maintenance of bones.
How are its levels controlled? When TSH acts on the thyroid gland, cells are stimulated to produce and release thyroxine and triiodothyronine. These hormones act on the pituitary gland and stop the production of TSH when levels are too high. They also act on the hypothalamus to stop production and secretion of thyrotropin-releasing hormone.
What happens when levels are too low? Very low levels of TSH an indicate that a person's thyroid glad is producing too much thyroid hormone, meaning that they have an overactive thyroid (hyperthyroidism). Very high levels of thyroid hormones will switch off the production and secretion of TSH. Hyperthyroidism will often manifest in unexplained weight loss, feeling hot, and even heart palpitations or anxiety. They can sometimes have a slightly enlarged thyroid gland. This can be treated through the use of medication that reduces thyroid gland activity and helps return thyroid hormone levels to normal. In rare cases, problems in the pituitary gland can also be responsible in low TSH and thus low free thyroid hormone levels.
What happens when levels are too high? High levels of TSH can indicate that a person's thyroid gland is not producing sufficient thyroid hormones, and thus has an underactive thyroid (hypothyroidism). Hypothyroidism will often manifest in feelings of lethargy, unexplained weight gain, and feeling cold easily, as well as goitre (an enlarged thyroid gland) in some cases. This can be treated through medication which restores thyroid hormone levels to normal, and thus reduces the amount of TSH in circulation. In rare cases, problems in the pituitary gland or genetic abnormalities can also result in elevated TSH levels, and thus high thyroid hormone levels.
Thyroxine (T4) + Triiodothyronine (T3)
What is it? Thyroxine (T4) is an inactive hormone released from the thyroid gland. Most of it is converted into the active form, triiodothyronine (T3) by other organs including the liver and kidneys.
Where is it produced? Thyroid hormones are produced in the thyroid gland. Approximately 20% of triiodothyronine is secreted into the bloodstream directly by thyroid gland, whilst the other 80% is produced from conversion of thyroxine.
Where and how does it act? What does it do? Thyroid hormones play a vital role in regulating the body's normal metabolic rate, heart and digestive functions, bone maintenance, and brain development.
How are its levels controlled? As already discussed, the production and release of thyroid hormones is controlled by a feedback loop system involving the hypothalamus, the pituitary gland, and the thyroid gland. When levels of thyroid hormones are low, the hypothalamus is triggered to produce and secrete thyrotropin-releasing hormone, which stimulates the pituitary gland to produce and secrete TSH. This in turn acts on the thyroid gland to produce and release thyroid hormones. When levels of these hormones increase too much, they act on the pituitary gland and hypothalamus to prevent the release of both thyrotropin-releasing hormone and TSH.
What happens when levels are too low? Low thyroid hormone production by the thyroid gland (hypothyroidism) can be caused by autoimmune diseases, low iodine intake, or the use of some medications. Thyroid hormones are essential for both physical and mental development, thus untreated hypothyroidism before birth or during childhood can result in detrimental mental impairment and reduced growth. In adults, hypothyroidism often results in low metabolism and symptoms including intolerance of cold temperatures, low heart rate, unexplained weight gain, reduced appetite, poor memory, depression, muscle stiffness, and reduced fertility.
What happens when levels are too high? High levels of thyroid hormones is known as thyrotoxicosis, and can be caused by overactivity of the thyroid gland in cases like Graves’ disease, a benign tumour, or thyroid inflammation. Thyrotoxicosis can be recognised by the presence of a goitre, which is a swelling and enlargement of the thyroid gland, and can also present with symptoms including unexplained weight loss, increased appetite, increased bowel movements, an irregular menstrual cycle, rapid/irregular heartbeat, tiredness, irritability, hair thinning, and tremor.
Christensen A, Bentley GE, Cabrera R, Ortega HH, Perfito N, Wu TJ, Micevych P. Hormonal regulation of female reproduction. Horm Metab Res.2012 Jul;44(8):587-91. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647363/.
Khan Academy. Estrogen. Available from: https://www.khanacademy.org/science/health-and-medicine/human-anatomy-and-physiology/reproductive-system-introduction/v/estrogen [Accessed 9 Dec 2018].
Mihma M, Gangooly S, Muttukrishna S. The normal menstrual cycle in women. Anim Reprod Sci. 2011 Apr;124(3-4):229-36. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20869180
O'Hara B. The HPO Axis. 2014 Aug 7. Available from: http://www.naturalfamilyplanning.ie/the-hpo-axis/ [Accessed 9 Dec 2018].
Adia Health. Your Hormones. Available from: https://adiahealth.com/app-content/your-hormones/ [Accessed 23 Jan 2019].