The endocrine and reproductive systems
The endocrine glands, from the hypothalamus and pituitary to the ovaries and testes, control the body through hormones that they release into the blood. A hormone acts only on cells that carry its receptor, its level is held by feedback, and too much or too little of it can cause disease. The reproductive organs belong with the glands because the gonads are endocrine organs and the reproductive cycle is run by their hormones and the pituitary's.
Endocrine glands and hormones
The endocrine system comprises specialised glands that secrete hormones directly into the blood or into the interstitial space, the fluid-filled space surrounding the cells of a tissue. These glands have no ducts, which is where the name endocrine, or "ductless", comes from. An exocrine gland, by contrast, secretes its product through a duct leading to the external environment, as oil, sweat and mammary glands do, and some organs, the pancreas among them, are both.
People in antiquity knew that the testes had powerful effects on the body without knowing how those effects were exerted. Males who lost them in childhood never went through puberty, kept their high voices, never grew a beard, did not go bald and tended to grow abnormally tall. During the Renaissance, anatomists began to suspect that other organs without visible ducts were also secreting something into the body: besides the testes and ovaries, the adrenals, thyroid, thymus and spleen. The puzzle of how such secretions reached distant sites was solved in 1628, when William Harvey suggested that blood circulates from the heart to the rest of the body and back, so that anything entering the bloodstream at any point could be carried everywhere.
A hormone is a chemical messenger released by an endocrine gland that affects cells in an organ in another part of the body, regulating the functions of other organs. The endocrine system is an integrated network of multiple organs releasing hormones that act on neighbouring or distant target cells.
The endocrine glands are widely distributed within the body: the hypothalamus, pituitary and pineal gland in the brain, the thyroid and parathyroids in the neck, the thymus in the chest, the pancreas and adrenal glands in the abdomen, and the ovaries and testes in the pelvis. They vary in size, and each has specialised cell types that produce and secrete specific hormones. Unlike the digestive or cardiovascular systems, the endocrine system does not consist of anatomically connected organs, and the glands instead communicate through hormones, which are manufactured and stored in the glands and released to act on neighbouring or distant target organs, meaning organs whose cells carry receptors specific for the hormone and respond when it binds. Those targets may be other endocrine glands or non-endocrine organs such as liver, kidney, bone and muscle.
Working with the kidneys and the nervous, immune, reproductive and digestive systems, the endocrine system helps maintain homeostasis and control many body functions, among them reproductive function, growth and development, sodium and water balance, blood volume and pressure, calcium and phosphate balance, energy balance and food metabolism, and the body's responses to stress. Its physiologic effects are wide-ranging, and many diseases can result from overproduction or underproduction of hormones, among them diabetes mellitus, infertility, Cushing syndrome and acromegaly.
The endocrine organs have the same general functions as the nervous system: communication, integration and control. The nervous system provides rapid, brief control through fast-travelling nerve impulses and helps maintain homeostasis by providing responses to immediate changes; the endocrine system provides slower but longer-lasting control through hormone secretion, and it controls the rate of development and maturation by secreting hormones slowly over long periods.
Hormone classes and receptors
Hormones fall into three main classes. Most are proteins or peptides, made of 3 to 200 amino acids and produced in the hypothalamus, pituitary, adrenal medulla and pancreas, such as growth hormone and insulin; some carry a carbohydrate component and are called glycoproteins, the pituitary's luteinizing and follicle-stimulating hormones among them. Steroid or lipid hormones are derived from cholesterol and made in the adrenal cortex, ovaries, testes and placenta: cortisol, oestrogen and testosterone. Monoamine hormones are derived from the amino acids tyrosine and tryptophan and made in the adrenal medulla and the thyroid: epinephrine, norepinephrine and the thyroid hormones.
A steroid is any of a group of lipids with a complex molecule of four interlocking carbon rings forming a hydrogenated cyclopentophenanthrene-ring system.
Some protein and peptide hormones are synthesised first as a larger molecule. A prohormone is such a precursor, usually a protein or peptide, with minimal biological activity and needing further processing to become active, and one prohormone can yield more than one active hormone: corticotropin, the opioid beta-endorphin and melanocyte-stimulating hormone all derive from a single precursor, pro-opiomelanocortin.
Hormone actions are classified into three types. Endocrine action means the hormone enters the bloodstream and acts on distant organs. Paracrine action means it is released into the interstitial space and acts on adjacent cells. Autocrine action means it acts on the surface receptors of the very cells that secreted it.
A target organ carries receptors specific to a particular hormone: the thyroid has receptors for the pituitary hormone thyrotropin and not for the pituitary's other hormones. A receptor is a structure, on the cell surface or within the cell, that recognises a particular hormone and produces a specific biological response, upregulatory or downregulatory, when that hormone binds to it.
There are two types of receptor, cell surface receptors and intracellular receptors. Protein and peptide hormones are too large to cross the cell membrane, so they bind receptors on the outside of the cell surface, and the hormone-receptor complex sets off a cascade of intracellular events ending in a specific biologic response such as the production of another hormone, an enzyme or another chemical. Steroid and thyroid hormones are much smaller, cross the membrane and bind intracellular receptors, and that complex binds DNA, activating or repressing gene expression and ultimately producing a specific biological response.
Control and feedback
Hormones are needed in minute amounts, so any excess or deficiency is quickly noticed, and they need to be secreted at the proper times during growth and development. Circulating concentrations are very small and usually have to be held within narrow limits: in the bloodstream, corticotropin ranges from 10 to 80 pg/mL and cortisol from 5 to 23 µg/dL.
Hormone production and release are controlled by the nervous system and by hormonal feedback mechanisms. Nervous system control of the endocrine system runs mainly through the hypothalamus, which is a neuroendocrine gland, neuroendocrine describing a cell type that secretes hormone into the bloodstream in response to a neural stimulus. The hypothalamus receives stimuli from the central and peripheral nervous systems and responds by producing hormones called neuropeptides or releasing hormones, which stimulate or inhibit the release of hormones from other endocrine glands, in particular the pituitary. A neuropeptide is a peptide hormone that is produced in the hypothalamus and transported to and released from the posterior pituitary. A releasing hormone is a hormone produced in the hypothalamus that controls the release of other hormones from the anterior pituitary. The endocrine system is also partly self-controlled, through mechanisms by which one hormone stimulates or inhibits the release of another. A hormone that stimulates the release of another is a tropic hormone.
Feedback in general is the transmission of evaluative or corrective information about an action, event or process to the original or controlling source. Hormonal control runs through feedback mechanisms, the process by which the concentration of one hormone in the blood can control the production and release of another, and the system has both negative and positive ones. In the negative case, pituitary thyrotropin stimulates the thyroid to release T3 and T4; when their blood levels are too low the pituitary makes more thyrotropin, and when they become too high the pituitary detects that and decreases thyrotropin production.
The thyroid loop begins one link further back, in the hypothalamus. When circulating T3 and T4 are low, the hypothalamus releases thyrotropin-releasing hormone (TRH) into the hypophyseal portal system, the vessels that carry blood from the hypothalamus to the anterior pituitary; in response, some cells of the anterior pituitary release thyrotropin, also called thyroid-stimulating hormone (TSH), which the bloodstream carries all over the body; and in the thyroid, TSH promotes the release of T4 and, to a lesser degree, T3. Some of the T4 is then converted to T3 in other tissues such as skeletal muscle, a conversion influenced by many hormones, TSH and adrenal hormones among them, and by nerve signals. Adequate or high T4 and T3 then suppress the release of TRH and TSH: without TRH the pituitary does not produce much TSH, and without TSH a healthy thyroid does not produce much T4 or T3. T4 and T3 are the system's outputs, but because they influence the hypothalamus they should also be regarded as inputs, and this process of outputs becoming inputs is called feedback. T4 and T3 suppress the processes that lead to their own secretion, a kind of suppression called negative feedback. Some hormones can have positive feedback effects under certain circumstances: before ovulation, oestrogen has a positive feedback effect on the hypothalamus and pituitary, the oestrogen produced by the ovary promoting the release of gonadotropin-releasing hormone, which stimulates the release of luteinizing hormone, which promotes the release of more oestrogen by the ovary.
The set of direct influences and feedback interactions among a set of endocrine glands is often called an axis, as in the hypothalamic-pituitary-thyroid axis. An axis is a combined system of neuroendocrine units that regulate the output of an endocrine gland.
Location, specificity and timing of a signal
The hypothalamic-pituitary-thyroid axis is one of many neuroendocrine regulatory systems, systems involving both nerve and endocrine tissue, which often interact with each other in complicated ways. Three general principles give them a basic context: the location, the specificity and the timing of the signal.
Location. A hormone is a signalling compound released into the bloodstream that carries a signal to some distant target tissue, and the distance matters: a house's temperature cannot be regulated by putting the thermostat inside the furnace, because the thermostat has to measure the effect the furnace is having in the living areas. In the same way, many bodily processes are regulated by hormones released by endocrine tissue distant from the process: the liver's storage or production of glucose is regulated by hormones from the pancreas, and the uptake of iron from the intestine by a hormone produced by the liver.
Specificity. A signalling system must provide a signal to the target cells and not to others, and there are three basic ways of achieving that. A nerve fibre provides a specific signal to a highly specific area of tissue; a vascular structure can carry the signal, as the hypophyseal portal vein carries small doses of hormone from the hypothalamus directly to the pituitary; and receptors on or in the cells of the target tissue make those cells selectively responsive. The presence of receptors on some cells and not others explains why a hormone affects some cells and not others, and differences in how the subtypes of a hormone's receptors are connected to the cell's internal signalling systems explain how the same hormone can have different effects on different kinds of cells.
Timing. A signal is useful only if it turns on and off in a timely manner. Neurotransmission is the fastest kind of signalling in the body: neurotransmitters have an immediate effect and may remain in the synapse for only a fraction of a second, so the neural signal has a rapid onset and a short duration. Many homeostatic mechanisms, such as those affecting blood sugar, do not need split-second timing but often have to act within minutes to maintain control over vital systems. Many of the hormones involved are peptide hormones, made of small chains of amino acids (typically fewer than 50 to 100), such as insulin and vasopressin, which tend to have a half-life of 10 to 20 minutes, meaning that half of the hormone's biological effect is lost by 10 to 20 minutes after secretion. Glycoprotein hormones, proteins with sugar molecules attached, such as follicle-stimulating and luteinizing hormone, tend to have a slightly longer half-life, 3 to 4 hours in the case of follicle-stimulating hormone. The steroid hormones, fat-soluble compounds derived from cholesterol and made by the sex glands and the adrenal glands, tend to have a longer half-life, estradiol's being approximately 13 to 20 hours.
The hypothalamus and the pituitary
The hypothalamus sits below the thalamus and just above the pituitary and is about the size of an almond in adults. It integrates neuronal and hormonal signals from outside the body (light, heat, cold) and from inside it (other brain regions and endocrine and non-endocrine organs) and produces an appropriate neuroendocrine response; one of its most important functions is to link the nervous system to the endocrine system by controlling the production and release of pituitary hormones. It is built of discrete cell clusters called nuclei, some secreting hormones that start and stop the production and release of the pituitary's own and carrying them to the anterior pituitary through a special set of blood vessels called the hypophyseal portal system, others sending their hormones along the long axons of those nuclei to the posterior pituitary.
The pituitary, also called the hypophysis, lies just below the hypothalamus in a bony hollow, the sella turcica, is about the size of a pea in adults, is divided into anterior and posterior parts, and is often called the master gland because of its effects on other organs. The anterior pituitary consists of five cell types that produce and store protein and peptide hormones: corticotrophs making corticotropin, formerly called adrenocorticotropic hormone; somatotrophs making growth hormone; lactotrophs making prolactin; thyrotrophs making thyrotropin, formerly called thyroid-stimulating hormone; and gonadotrophs making luteinizing hormone and follicle-stimulating hormone.
The releasing hormones travel through blood vessels to the anterior pituitary, where each controls the production and release of one or more pituitary hormones, and each pituitary hormone in turn affects the function of one or more target glands or organs. Corticotropin-releasing hormone controls corticotropin, which controls cortisol release from the adrenal gland. Gonadotropin-releasing hormone controls both follicle-stimulating hormone and luteinizing hormone, which control production of testosterone, oestrogen and progesterone in the testes and ovaries. Growth hormone release is stimulated by growth hormone-releasing hormone and inhibited by somatostatin, and growth hormone regulates growth, development and energy metabolism. Thyrotropin-releasing hormone stimulates the release of both thyrotropin and prolactin, thyrotropin making the thyroid release more thyroid hormone and prolactin stimulating milk production.
Adrenocorticotropic hormone (ACTH), the older name for corticotropin, makes the adrenal cortex increase in size and secrete more of its hormone; follicle-stimulating hormone (FSH) stimulates production of ova and sperm; luteinizing hormone (LH) stimulates ova to mature and causes ovulation, and stimulates the testes to secrete testosterone; melanocyte-stimulating hormone (MSH) causes a rapid increase in the synthesis and dispersion of melanin; and prolactin (PRL) stimulates breast development and milk secretion after birth.
The posterior pituitary stores and secretes two hormones made in the hypothalamus, oxytocin and antidiuretic hormone, also called arginine vasopressin, which travel down the long axons of the hypothalamic neurosecretory cells. Antidiuretic hormone increases water reabsorption from the kidneys, accelerating resorption of water from urine in the kidney tubules, and so is important in controlling plasma osmolality. Oxytocin promotes uterine contractions during labour and delivery and stimulates milk ejection in lactating women, and it is also thought to affect behaviour.
Diseases caused by pituitary malfunction usually result from hormone-producing pituitary adenomas, benign tumours that have the potential to cause serious health complications by producing large amounts of hormone in a way the usual feedback mechanisms do not regulate. The commonest are prolactinomas, growth-hormone-secreting tumours and corticotropin-producing tumours: a prolactinoma can cause excessive milk production and reproductive dysfunction, excess growth hormone can cause acromegaly in adults and gigantism in children, and excess corticotropin can cause excessive cortisol production (Cushing syndrome), central obesity, hypertension and hyperglycaemia. Diseases resulting from reduced levels of pituitary hormones include diabetes insipidus, a condition in which the kidneys cannot conserve water, caused by a lack of antidiuretic hormone from the posterior pituitary.
Growth hormone
Growth hormone stimulates general body growth, and it has a wide range of effects on the liver, skeletal muscle, bone and adipose tissue. Produced by the anterior pituitary under the opposing control of growth hormone-releasing hormone and somatostatin, it is secreted in a pulsatile fashion at three- to five-hour intervals across a 24-hour period, with a surge released after about an hour of deep sleep. In the liver it stimulates the production of glucose, decreases the uptake of glucose from blood, and stimulates production of insulin-like growth factor 1, another growth-promoting hormone. During childhood and adolescence it increases body height, and throughout life it increases calcium retention in bone and promotes bone mineralisation. In skeletal muscle it increases muscle mass and protein synthesis and decreases glucose uptake. In adipose tissue it stimulates the breakdown of triglycerides, suppresses the uptake and accumulation of circulating lipids, and reduces glucose uptake.
Both overproduction and underproduction of growth hormone can be problematic. Too much leads to gigantism in children and acromegaly in adults, the latter characterised by soft tissue swelling that enlarges the hands, feet, nose, lips and ears and by a general thickening of the skin. Overproduction is usually caused by a growth-hormone-secreting tumour of the pituitary. Deficiency in children can lead to dwarfism, whose cause can be congenital, head trauma, or damage to the hypothalamus or pituitary caused by treatment of tumours of the head.
The thyroid and parathyroid glands
The thyroid is a butterfly-shaped, two-lobed organ in the neck in front of the trachea and below the Adam's apple. In response to thyrotropin from the pituitary it produces two hormones, triiodothyronine (T3), which contains three iodine atoms, and thyroxine (T4), which contains four. T3 and T4 have effects throughout the body: they stimulate cellular metabolism, are involved in regulating body metabolism, body heat and oxygen consumption, and are important for growth and development during childhood.
T4 and T3 stimulate the basal metabolic rate: body temperature rises, the heart beats harder and faster, stored nutrients are released from the liver and muscles, and stimulation of the nervous system brings higher levels of attention and quicker reflexes, while in children the hormones promote brain development as well as growth. The balance of thyroid hormone levels is critically important because too much is bad and so is too little.
The thyroid is also important in controlling calcium and phosphorus: on sensing high blood calcium it produces calcitonin, which inhibits the release of calcium from bone into the bloodstream and inhibits absorption of calcium by the intestines, thereby lowering blood calcium, and which also inhibits phosphate reabsorption in the kidney.
The parathyroid glands work with the thyroid to maintain normal blood levels of calcium and phosphorus. There are usually four, each about the size of a grain of rice, embedded behind the thyroid with two on each lobe; they help control calcium and phosphate levels and are also important for normal bone development. On sensing low blood calcium they make parathyroid hormone, which causes the release of calcium from bone into the bloodstream and the reabsorption of calcium in the kidney, raising blood calcium, and which also decreases the reabsorption of phosphate in the kidney. Together the two hormones hold blood calcium between 9 and 11 mg per 100 mL. Rising calcium prompts the thyroid to release calcitonin, which stimulates calcium salt deposition in bone, and falling calcium prompts the parathyroid glands to release parathyroid hormone, with osteoclasts degrading bone matrix and releasing calcium into the blood.
Underproduction of the thyroid hormones is hypothyroidism, most often caused by an autoimmune disease leading to chronic inflammation of the gland, and less commonly by acute inflammation, by insufficient thyrotropin from the pituitary, or by drugs given for other conditions that affect thyroid function; it slows the body's metabolism, and in children delays development and growth. Overproduction is hyperthyroidism, most commonly caused by an autoimmune disease or by thyroid growths called nodules that produce too much hormone and rarely by inflammation of the gland, and it can cause rapid heartbeat, intolerance to heat and weight loss. Overproduction of parathyroid hormone can be caused by primary or secondary hyperparathyroidism: in primary hyperparathyroidism a noncancerous tumour secretes the hormone or enlarged glands produce more of it than normal, while in secondary hyperparathyroidism the glands are normal and secrete too much because blood calcium is low, which chronic kidney failure and other conditions can cause.
If something goes wrong in any portion of the hypothalamic-pituitary-thyroid axis, thyroid hormone levels can be too low or too high. Hypothyroidism can arise in the thyroid gland itself, as after thyroid surgery or in autoimmune thyroiditis; from a lack of TSH when the anterior pituitary fails; or from problems involving the hypothalamus: disruption of the hypophyseal portal vein would prevent TRH from reaching the anterior pituitary, and starvation or other serious illness may cause the hypothalamus to alter the set point of thyroid homeostasis. Hyperthyroidism usually results from a problem in the thyroid gland but can also result from a TSH-secreting tumour of the pituitary, and abnormally high T4 can also come from eating animal thyroid tissue or from an overdose of thyroid replacement pills. The first step in diagnosing a disorder of the axis is to measure blood levels of T4, T3 and TSH. If the thyroid cannot produce enough hormone, T4 and T3 are low but TSH is high, as the hypothalamus and pituitary try to correct the problem; if the problem is in the hypothalamus or pituitary, TSH is low; and in hyperthyroidism TSH is low when overactive thyroid tissue is the cause but high when the cause is a TSH-secreting pituitary adenoma.
The adrenal glands
The adrenal glands are a pair, one on top of each kidney, and each has two distinct hormone-producing regions: an outer cortex that makes steroid hormones and an inner medulla that makes the catecholamines epinephrine and norepinephrine. The cortex produces three classes of steroid hormone (mineralocorticoids such as aldosterone, androgens such as testosterone, and glucocorticoids such as cortisol) in three functionally distinct layers: the thin outer zona glomerulosa, the middle zona fasciculata and the innermost zona reticularis. Mineralocorticoids such as aldosterone control minerals in the blood, glucocorticoids such as hydrocortisone help maintain normal blood glucose concentration, and the sex hormones are responsible for secondary sexual characteristics.
A corticosteroid, also called a corticoid, is any of the steroid hormones produced by the adrenal cortex, or their synthetic equivalents, and a glucocorticoid is any corticoid that increases gluconeogenesis, thus raising blood glucose.
Aldosterone, produced by the cells of the zona glomerulosa, is involved in the control of blood volume and kidney function; its secretion can be stimulated by many factors, among them increases in angiotensin II, corticotropin and plasma potassium and a decrease in blood pressure, and it acts on the kidneys to promote retention of sodium and water, excretion of potassium and increased blood volume, raising blood pressure. Cortisol, produced by the cells of the zona fasciculata in response to corticotropin from the anterior pituitary, helps the body respond to stress by increasing blood glucose and breaking down protein and fat, and its secretion follows a circadian rhythm linked to the sleep-wake cycle: in someone with a fairly consistent sleep schedule, corticotropin and subsequently cortisol levels increase during the third to fifth hours of sleep, with maximal cortisol secretion an hour after waking. Adrenal androgens are produced in negligible amounts beside those from the gonads.
The medulla's two catecholamines are released in response to stressors such as excitement, fear, unexpected noise and physical threats and help mediate the fight-or-flight reaction, and they stimulate the general adaptation syndrome. Epinephrine is responsible for fight-or-flight responses, increasing heart and respiratory rates and causing muscle contraction, while norepinephrine helps maintain normal physiologic processes including heart function.
Abnormal adrenal function can arise when the pituitary makes too much or too little corticotropin, and when the adrenal gland does not make enough hormone or secretes too much. Prolonged exposure to high cortisol levels causes Cushing syndrome, characterised by weight gain particularly in the trunk and face, and excess cortisol can also cause excessive sweating, reduced libido and impotence in men, and amenorrhoea and infertility in women. Those conditions are sometimes temporary and caused by taking certain medications, and can also be caused by pituitary gland disorders such as tumours or other damage, by autoimmune disease, or by adrenal gland tumours.
The pancreas and blood glucose
The pancreas lies behind the stomach and duodenum and is both an endocrine and an exocrine organ: its islets of Langerhans make insulin and glucagon, and as an exocrine organ it secretes pancreatic juice, which contains digestive enzymes, through the pancreatic duct into the small intestine, where the juice aids digestion. It has a central role in energy metabolism, use and storage. Within the islets, insulin comes from the beta cells and glucagon from the alpha cells. Insulin has anabolic effects, meaning constructive metabolic ones, promoting synthesis of carbohydrate, fat and protein and decreasing blood glucose concentrations, and glucagon has catabolic, destructive, effects that increase them.
High blood glucose stimulates insulin production, which increases the entry of glucose into muscle, fat and liver cells, where it is converted into metabolic energy in muscle cells and used for the synthesis of fat in fat cells and of glycogen, a carbohydrate that stores energy, in muscle and liver cells. Low blood glucose stimulates glucagon production, and in the liver glucagon stimulates the breakdown of glycogen into glucose, which is released into the bloodstream. Working together, the two hormones hold blood glucose at a normal level of about 90 mg per 100 mL. A rise, as after a meal, sets off insulin release and a fall, as after a skipped meal, sets off glucagon release, and the stimulus for each hormone's release diminishes as blood glucose returns to that set point.
The pineal gland and the thymus
The pineal gland, about the size of a pea, sits in the brain behind the thalamus and is sometimes called the third eye for its role in regulating sleep-wake cycles and seasonal functions. It produces melatonin, which has a role in modulating circadian rhythms and promotes drowsiness and sleep; its production is stimulated by darkness and inhibited by light. Cells in the retina detect ambient light and send a signal to the suprachiasmatic nucleus of the hypothalamus, which regulates the 24-hour circadian rhythm; neuronal circuits run from there to clusters of cells called the paraventricular nuclei, then to the superior cervical ganglia and finally to the pineal gland. In some animals melatonin levels influence hibernation and seasonal breeding. Melatonin mediates sleep and ovulation cycles. Several types of pineal tumour have been associated with abnormal onset of puberty in children. As of 2013, attempts to correlate melatonin levels with disease occurrence needed more data to confirm causal relationships.
The thymus lies in the chest cavity behind the sternum, is largest at puberty, and then diminishes in size and is replaced by fatty tissue in adults. It secretes hormones called humoral factors, which stimulate the development of the lymphoid system. It also produces and secretes hormones called thymosins.
The reproductive system
While the other body systems are concerned primarily with survival of the individual, the reproductive systems are concerned with survival of the species. The human reproductive system produces, stores, nourishes and transports functional gametes, and its components are the gonads, ducts, accessory glands and external genitalia. The gonads are the organs that make gametes, the specialised cells for reproduction: the ovaries and the testes.
The male reproductive system includes the testes, epididymis, ductus deferens, ejaculatory duct, seminal vesicles, prostate and bulbourethral glands. The female reproductive system includes the ovaries, uterine tubes, uterus, vagina and various accessory glands.
The ovaries and testes are endocrine organs as well as gonads. The ovaries are a pair of oval structures each about the size of a large olive in the pelvic cavity; their granulosa cells produce oestrogens and progesterone, which help control reproductive function in women, and they produce ova, which are stored and mature there. The testes are a pair of ellipsoid organs in the scrotum averaging 18 cm³ each, with sperm produced, stored and maturing in the Sertoli cells and androgens including testosterone, which help control reproductive function in men, produced by the Leydig cells.
Sex hormones and the menstrual cycle
Testosterone is the primary male sex hormone and it masculinises: male characteristics such as a deep voice occur because of it. It also promotes and maintains the development of the male accessory organs and stimulates protein metabolism. Testosterone and its metabolites are responsible for male sexual development (including descent of the testes from the abdominal cavity to the scrotum, which normally occurs before birth, growth and maturation of the male reproductive organs, and stimulation of spermatogenesis) and for growth of the larynx and deepening of the voice during puberty, inhibition of breast development, anabolic effects on muscle, and male-pattern baldness. The testes are regulated by luteinizing and follicle-stimulating hormone from the pituitary, and their main functions are testosterone production and spermatogenesis, the formation and development of the male gametes, spermatozoa, in the testes.
Oestrogen and progesterone are the primary female sex hormones. Oestrogen develops and maintains female characteristics such as breasts, and stimulates epithelial cells to reproduce themselves, especially in the lining of the uterus. Progesterone stimulates secretion by the epithelial cells of the uterine lining, provided oestrogens have previously acted on them, and decreases contractions by the uterine muscles. The placenta also produces oestrogen and progesterone, with the same functions as those from the ovary, and oestrogen mediates the development and maintenance of the accessory sex organs and stimulates reproduction of the uterine lining. Beyond its reproductive effects, oestrogen stimulates the growth and proliferation of breast tissue, influences mood, provides protective effects for the heart, protects against bone loss and may protect against colon cancer.
The menstrual cycle is the monthly cycle in which an egg is released from an ovary, the endometrial lining of the uterus prepares for pregnancy, and that lining is shed if pregnancy does not occur. Luteinizing hormone and follicle-stimulating hormone stimulate oestrogen and progesterone production in the ovaries and together control the cycle. In the first part of the cycle, the follicular phase, follicle-stimulating hormone is responsible for the recruitment and growth of an ovarian follicle while luteinizing hormone acts on the follicle's granulosa cells to stimulate oestrogen production. The rising oestrogen stimulates the pituitary to release more luteinizing hormone, which stimulates still more oestrogen, and so produces the surge of luteinizing hormone that ovulation requires; this is positive feedback. In the second part, the luteal phase, luteinizing hormone is responsible for forming the corpus luteum from the remnants of the ovulatory follicle and for the oestrogen and progesterone it produces, and progesterone acts on the reproductive tract to prepare it for the initiation and maintenance of pregnancy.
Approximately 25% of female infertility cases are due to ovulation that is absent or infrequent, and the hormonal causes of insufficient ovulation include polycystic ovary syndrome, insufficient gonadotropin-releasing hormone, hyperprolactinaemia, which affects oestrogen levels, and primary ovarian insufficiency, a lack of oestrogen. An overactive or underactive thyroid gland, diabetes mellitus and obesity can also affect fertility. In boys and men, decreased testosterone production, or hypogonadism, can be caused by disorders of the hypothalamus or pituitary or by testicular dysfunction. Low testosterone in early childhood results in short stature, no deepening of the voice, a female pattern of secondary hair, and underdeveloped muscles and genitalia with delayed or absent onset of sexual maturation. Testosterone deficiency in adults alters body composition with muscle weakness and atrophy, changes mood and cognitive function, and causes regression of sexual function and spermatogenesis.
Treatment of endocrine disease
Many endocrine diseases result from the over- or underproduction of some hormone. Overproduction is often due to a functional tumour, which can often be removed surgically, and other ablative methods can also be used, as when hyperthyroidism is treated with a dose of radioactive iodine, which is taken up by and destroys thyroid tissue, after which the patient requires hormone replacement therapy. Underproduction is often treated by hormone replacement.
Protein hormones such as insulin and glycoprotein hormones such as follicle-stimulating hormone generally have to be given by injection, because they would be digested in the stomach if taken by mouth; one exception is desmopressin, a peptide hormone that can be given orally or intranasally. Steroid hormones can also be given by mouth, although a portion of an oral dose is broken down in the liver before it reaches the general circulation. Drugs with hormone-like effects are often used to treat endocrine disease and for other purposes. Sometimes they are used for purposes other than hormone replacement.
A hormone drug's effect on the body's hormonal balance can be hard to predict, because the drug can act on various feedback loops. Glucocorticoid drugs tend to suppress the hypothalamus's production of corticotropin-releasing hormone, which suppresses the pituitary's release of corticotropin, which in turn suppresses the adrenal glands' release of cortisol; for that reason glucocorticoid drugs should not be stopped abruptly but tapered, to allow the hypothalamic-pituitary-adrenal axis to return to normal. In a healthy person the endocrine glands interact in complicated ways to promote growth, maintenance and reproduction, so disorders of the glands can have complicated effects on the body.