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Introduction to the endocrine system part 2: physiology.

The endocrine system has a vital role in maintaining homeostasis and controlling a wide range of body functions.

It is a network of anatomically distinct organs (endocrine glands) that communicate with each other through chemical messengers called hormones. Each endocrine gland has specialized cell types that produce and secrete specific hormones. Hormone production and release are controlled by the nervous system and by hormonal feedback mechanisms. Through these hormones and feedback mechanisms, the endocrine system interacts with other organs and body systems, including the kidneys, the nervous system, the immune system, the reproductive system, and the digestive system, to help maintain homeostasis and control many physiologic processes.


The hypothalamus is a portion of the brain that integrates neuronal and hormonal signals from both external sources (environmental signals such as light, heat, and cold) and internal sources (other brain regions, endocrine organs, and nonendocrine organs) and produces an appropriate neuroendocrine response. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system by controlling the production and release of hormones from the pituitary gland.

The neurosecretory cells of the hypothalamus produce both neuropeptides and releasing hormones. The neuropeptides, which include antidiuretic hormone and oxytocin, travel down the long axons of the cells and are released from the posterior pituitary gland. Antidiuretic hormone increases water reabsorption from the kidneys and thus is important in controlling plasma osmolality. Oxytocin promotes uterine contractions during labor and delivery and stimulates milk ejection in lactating women. Oxytocin is also thought to affect behavior.

The releasing hormones travel through blood vessels to the anterior pituitary, where they stimulate the release of pituitary hormones. Each releasing hormone controls the production and release of one or more pituitary hormones, and each pituitary hormone affects the function of one or more target glands or organs (Figure 1). A hypothalamic hormone, corticotropin-releasing hormone, controls the release of corticotropin from the anterior pituitary gland. In turn, corticotropin controls the release of cortisol from the adrenal gland. Gonadotropin-releasing hormone controls two pituitary hormones: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH control the production of the reproductive hormones testosterone, estrogen, and progesterone in the testes and ovaries. Growth hormone (GH) release from the pituitary gland is stimulated by GH-releasing hormone and is inhibited by somatostatin. In turn, GH regulates growth and development, and energy metabolism. Thyrotropin-releasing hormone stimulates the release of both thyrotropin and prolactin. Thyrotropin controls thyroid hormone release from the thyroid gland, and prolactin stimulates milk production.

Disease States

Diseases caused by pituitary gland malfunction usually result from hormone-producing pituitary adenomas. Adenomas are benign tumors that have the potential to cause serious health complications by producing large amounts of hormones in a manner that is not regulated by the usual feedback mechanisms. The most common types of pituitary adenomas are prolactinomas, GH-secreting tumors, and corticotropin-producing tumors. Prolactinomas can cause excessive milk production and reproductive dysfunction. (1) Excess GH can cause acromegaly in adults and gigantism in children. (2) Excess corticotropin can cause excessive cortisol production (Cushing syndrome), central obesity, hypertension, and hyperglycemia. (3) Diseases resulting from a reduced level of pituitary hormones include diabetes insipidus (a condition in which the kidneys cannot conserve water), which is caused by a lack of antidiuretic hormone from the posterior pituitary.


ovaries and testes

The ovaries are the female reproductive organs. LH and FSH stimulate the production of estrogen and progesterone in the ovaries and, together, control the menstrual cycle. During the first part of the menstrual cycle (the follicular phase), FSH is responsible for the recruitment and growth of an ovarian follicle. LH acts on the granulosa cells of the follicle to stimulate the production of estrogen. Increasing levels of estrogen stimulate the release of more LH from the pituitary, resulting in a surge of LH, which is required for ovulation. During the second part of the cycle (the luteal phase), LH is responsible for the formation of the corpus luteum from the remnants of the ovulatory follicle and for the production of estrogen and progesterone from the corpus luteum. Progesterone acts on the reproductive tract to prepare it for the initiation and maintenance of pregnancy. In addition to its reproductive effects, estrogen 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 male reproductive organs, the testes, are also regulated by LH and FSH from the pituitary gland. The main functions of the testes are testosterone production and spermatogenesis. Testosterone and its metabolites are responsible for male sexual development--including the descent of the testes from the abdominal cavity to the scrotum (which normally occurs before birth), growth and maturation of male reproductive organs, and stimulation of spermatogenesis--and for the growth of the larynx and deepening of the voice during puberty, inhibition of breast development, anabolic effects on muscle, and male-pattern baldness.

Disease States

Approximately 25% of female infertility cases are due to ovulation that is absent or infrequent. Hormonal causes of infertility resulting from insufficient ovulation include polycystic ovary syndrome, insufficient gonadotropin-releasing hormone, hyperprolactinemia (which affects estrogen levels), and primary ovarian insufficiency (lack of estrogen). An overactive or underactive thyroid gland, diabetes mellitus, and obesity can also affect fertility. (4)

In boys and men, decreased testosterone production (ie, hypogonadism) can be caused by disorders of the hypothalamus or pituitary or by testicular dysfunction. Low levels of testosterone in early childhood result in short stature, lack of deepening of the voice, female pattern distribution of secondary hair, and underdeveloped muscles and genitalia with delayed or absent onset of sexual maturation. Testosterone deficiency in adults leads to an alteration in body composition associated with muscle weakness and atrophy, changes in mood and cognitive function, and regression of sexual function and spermatogenesis.


The paired adrenal glands have two distinct hormone-producing regions. The outer region of the gland, the cortex, produces three types of steroid hormones: mineralocorticoids (aldosterone), androgens (testosterone), and glucocorticoids (cortisol). The inner region, the medulla, produces catecholamines (epinephrine and norepinephrine). The adrenal cortex has three functionally distinct layers, each of which produces different steroid hormones: the thin outer zona glomerulosa, the middle zona fasciculata, and the innermost region, the zona reticularis.

Aldosterone, involved in the control of blood volume and kidney function, is produced by the cells of the zona glomerulosa. Aldosterone secretion can be stimulated by many factors, including increases in angiotensin II, corticotropin, and plasma potassium levels, and a decrease in blood pressure. Aldosterone acts on the kidneys to promote retention of sodium and water, excretion of potassium, and increased blood volume, leading to increased blood pressure.

In response to corticotropin secretion from the anterior pituitary gland, the cells of the zona fasciculata produce cortisol, a glucocorticoid hormone. A circadian rhythm of cortisol secretion in humans is linked to a person's sleep-wake cycle. In individuals with a fairly consistent sleep schedule, corticotropin and subsequently cortisol levels increase during the third to fifth hours of sleep, with the maximal cortisol secretion occurring an hour after waking. Cortisol helps the body respond to stress by causing an increase in blood glucose levels and a breakdown of protein and fat. Androgens, including testosterone, are produced by the adrenal cortex, but the amount is negligible compared with that produced by the gonads.

The inner part of the adrenal gland, the medulla, produces the catecholamines epinephrine and norepinephrine. These two hormones are released in response to stressors such as excitement, fear, unexpected noise, and physical threats. Epinephrine is responsible for fight-or-flight responses, which cause increased heart and respiratory rates, and muscle contraction. Norepinephrine helps maintain normal physiologic processes, including heart function.

Disease States

Abnormal adrenal function can arise when the pituitary gland makes too much or too little corticotropin and when the adrenal gland either does not make enough hormone or secretes too much. Prolonged exposure to high cortisol levels causes Cushing syndrome, which is characterized by weight gain, particularly in the trunk and face. Excess cortisol levels can also cause excessive sweating, reduced libido, and impotence in men, and amenorrhea and infertility in women. Sometimes these conditions are temporary and are caused by taking certain medications. These conditions can also be caused by pituitary gland disorders (tumors or other damage), autoimmune disease, or adrenal gland tumors. (3,5,6)


The pancreas has a central role in energy metabolism, use, and storage. Specialized cells within the pancreas, the islets of Langerhans, produce two hormones, insulin (produced by the [beta] cells) and glucagon (produced by the [alpha] cells). Insulin has anabolic effects that promote the synthesis of carbohydrate, fat, and protein, and decrease blood glucose concentrations. Glucagon has catabolic effects that increase blood glucose concentrations. Working together, these two hormones control blood glucose levels (Figure 2). High blood glucose levels stimulate the production of insulin, which increases the entry of blood glucose into muscle, fat, and liver cells. The glucose is then converted into metabolic energy (in muscle cells) and is used for the synthesis of fat (in fat cells) and glycogen (in muscle and liver cells). Glycogen is a carbohydrate that serves as a form of energy storage in muscle and liver cells. Low blood glucose levels stimulate the production of glucagon from the pancreas. In the liver, glucagon stimulates the breakdown of glycogen into glucose, which is then released into the bloodstream, causing blood glucose levels to increase.


Disease States

The most common disease resulting from impaired pancreatic hormone release is diabetes mellitus, which is the result of insufficient insulin. An estimated 23 million people in the United States have diabetes mellitus, including approximately 5 million with undiagnosed diabetes mellitus. (7) The two main forms of diabetes mellitus are type 1 and type 2. Type 1 diabetes mellitus, also known as insulin-dependent diabetes, accounts for about 5% of diabetes cases. It results from beta-cell destruction and can be treated with insulin. Type 2 diabetes mellitus accounts for about 95% of diabetes cases and results from a combination of insufficient insulin production and insulin resistance (impairment of the body's ability to use insulin). It is frequently associated with obesity and lack of exercise.


Produced by the anterior pituitary gland, GH is under the control of two hypothalamic hormones: GH-releasing hormone, which stimulates GH release, and somatostatin, which inhibits GH release. GH is secreted in a pulsatile fashion in 3- to 5-hour intervals during a 24-hour period, with a surge of GH released after about an hour of deep sleep. GH has a wide range of effects on the liver, skeletal muscle, bone, and adipose tissue. In the liver, GH stimulates the production of glucose, decreases the uptake of glucose from blood, and stimulates the production of another growth-promoting hormone, insulin-like growth factor 1. During childhood and adolescence, GH increases body height; throughout a person's lifetime, GH increases calcium retention in bone and promotes bone mineralization. In skeletal muscle, GH increases muscle mass, increases protein synthesis, and decreases glucose uptake. GH stimulates the breakdown of triglycerides, suppresses the uptake and accumulation of circulating lipids, and reduces glucose uptake in adipose (fatty) tissue.

Disease States

Both overproduction and underproduction of GH by the pituitary gland can be problematic. Too much GH leads to gigantism in children and to a disease called acromegaly in adults. Acromegaly is characterized by soft tissue swelling that results in enlargement of the hands, feet, nose, lips, and ears, and a general thickening of the skin. The overproduction of GH is usually caused by a GH-secreting tumor of the pituitary gland. Deficiency of GH in children can lead to dwarfism; the cause can be congenital, head trauma, or damage to the hypothalamus or pituitary gland caused by treatment of tumors of the head. (8)



In response to the secretion of thyrotropin from the pituitary gland, the thyroid gland produces two hormones, triiodothyronine ([T.sub.3]) and thyroxine ([T.sub.4]). Both [T.sub.3] and [T.sub.4] have effects throughout the body and are involved in regulating body metabolism, body heat, and oxygen consumption. In addition, [T.sub.3] and [T.sub.4] are important for growth and development during childhood. The thyroid gland is also important in controlling calcium and phosphorus levels in the body. Upon sensing high blood calcium levels, the thyroid gland produces the hormone calcitonin, which inhibits the release of calcium from bone into the bloodstream and inhibits the absorption of calcium by the intestines, thereby lowering calcium levels (Figure 3). Calcitonin also inhibits phosphate reabsorption in the kidney.

Disease States

The underproduction of [T.sub.3] and [T.sub.4] is called hypothyroidism. Hypothyroidism is most often caused by an autoimmune disease that leads to chronic inflammation of the thyroid gland. Less common causes of hypothyroidism include acute inflammation of the thyroid gland, insufficient thyrotropin produced by the pituitary gland, and drugs for other conditions that affect thyroid function. (9) Hypothyroidism slows the body's metabolism. In children, development and growth are delayed.

Hyperthyroidism occurs when too much [T.sub.3] and [T.sub.4] are produced. This excess hormone production is most commonly caused by an autoimmune disease or by thyroid growths (called nodules) that produce too much hormone; rarely, hyperthyroidism is caused by inflammation of the gland. (10) Hyperthyroidism can cause rapid heartbeat, intolerance to heat, and weight loss.


The parathyroid glands work with the thyroid gland to maintain normal blood levels of calcium and phosphorus. In humans, the four parathyroid glands are embedded behind the thyroid gland. Upon sensing low blood calcium levels, the parathyroid glands make parathyroid hormone (PTH), which causes the release of calcium from bone into the bloodstream and the reabsorption of calcium in the kidney, thereby increasing the blood levels of calcium (Figure 3). Parathyroid hormone also decreases the reabsorption of phosphate in the kidney.

Disease States

Overproduction of PTH can be caused by primary or secondary hyperparathyroidism. Primary hyperparathyroidism occurs when a noncancerous tumor secretes PTH or when enlarged parathyroid glands produce more PTH than normal. (11) In secondary hyperparathyroidism, the parathyroid glands are normal, but they secrete too much PTH because of low blood levels of calcium, which can be caused by chronic kidney failure or other conditions.


The pineal gland produces the hormone melatonin, which promotes drowsiness and sleep. Melatonin production is stimulated by darkness and inhibited by light. Cells in the retina of the eye detect ambient light and send a signal to an area of the hypothalamus called the suprachiasmatic nucleus, which regulates the 24-hour circadian rhythm. Neuronal circuits from the suprachiasmatic nucleus connect to clusters of cells called the paraventricular nuclei. The signal then travels to the superior cervical ganglia and finally to the pineal gland. In some animals, melatonin levels influence hibernation and seasonal breeding.

Disease States

Several different types of pineal gland tumors have been associated with abnormal onset of puberty in children. Scientists have attempted to correlate melatonin levels with disease occurrences, but more data are needed to confirm causal relationships. (12)


The thymus gland is where T lymphocytes (also called T cells) mature early in life. If the thymus does not develop or is removed during childhood, the immune system will not develop completely. The thymus produces and secretes hormones called thymosins. T lymphocytes become immunologically active when they interact with thymosins either inside the thymus or in the bloodstream.

Disease States

If the thymus does not develop (as in DiGeorge syndrome (13)), the immune system is mildly to moderately deficient.


The endocrine system works with other body systems to control and coordinate many physiologic processes, including reproductive function, growth and development, maintenance of homeostasis, and responses to stress. Overproduction or underproduction of hormones can lead to diseases such as diabetes mellitus, infertility, Cushing syndrome, and acromegaly.


anabolic--Involving constructive metabolic processes.

catabolic--Involving destructive metabolic processes.

endocrine gland--A ductless gland that

produces hormones and releases them into the circulation (eg, ovaries, pancreas, pituitary gland).

endocrine system--An integrated network of multiple organs that release hormones that exert their effects on neighboring or distant target cells.

feedback mechanisms--The process by which the concentration of one hormone in the blood can control the production and release of another hormone. There are positive feedback mechanisms and negative feedback mechanisms in the endocrine system.

homeostasis--The maintenance of internal conditions within a normal range by a living organism.

hormone--A chemical that is released by an endocrine gland and affects cells in an organ in another part of the body (eg, estrogen, growth hormone, insulin).

menstrual cycle--The monthly cycle in which an egg is released from an ovary, the endometrial lining of the uterus prepares for pregnancy, and the endometrial lining is shed if pregnancy does not occur.

neuroendocrine--A cell type that secretes hormones into the bloodstream in response to a neural stimulus (eg, the hypothalamus is a neuroendocrine gland).

spermatogenesis--The formation and development of male gametes, called spermatozoa, in the testes.

Author disclosure: The authors note that they have no commercial associations that may pose a conflict of interest in relation to this article.

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(1.) Klibanski A, Schlechte J, eds. Hyperprolactinemia fact sheet. Hormone Health Network of The Endocrine Society. www.hormone. org/Resources/upload/FS_APD_ Hyperprolactinemia_EN-6-12.pdf. Published January 2010. Accessed February 25, 2013.

(2.) Cook D, Freda P, Trainer P, eds. Acromegaly fact sheet. Hormone Health Network of The Endocrine Society. Resources/upload/FS_APD_ Acromegaly_EN-web.pdf. Published January 2012, 4th edition. Accessed February 25, 2013.

(3.) Findling J, Young W Jr, eds. Cushing's syndrome fact sheet. Hormone Health Network of The Endocrine Society. FS_APD_Cushings_Syndrome_EN-612.pdf. Published January 2012, 4th ed. Accessed February 25, 2013.

(4.) Lobo R, Martin K, eds. Infertility and women fact sheet. Hormone Health Network of The Endocrine Society. upload/FS_MWH_Infertility_Women_ EN-6-12.pdf. Published January 2012, 4th ed. Accessed February 25, 2013.

(5.) Arafah B, Auchus R, eds. Adrenal insufficiency fact sheet. Hormone Health Network of The Endocrine Society. Other/upload/FS_APD_Adrenal_ Insufficiency_EN-6-12.pdf. Published August 2010. Accessed February 25, 2013.

(6.) Stewart P, Young W, eds. Primary aldosteronism fact sheet. Hormone Health Network of The Endocrine Society. Resources/upload/FS_APD_ Primary_Aldosteronism_EN-6-12-2. pdf. Published March 2012, 3rd ed. Accessed February 25, 2013.

(7.) Diabetes. Hormone Health Network of The Endocrine Society. www. cfm. Accessed February 25, 2013.

(8.) Merriam G, Molitch M, eds. The Hormone Foundation's patient guide to growth hormone deficiency in adults. The Endocrine Society. www. PG-GHD-Adults-Web.pdf. Published June 2011, 2nd ed. Accessed February 25, 2013.

(9.) Cooper D, McDermott M, Wartofsky L, eds. Hypothyroidism fact sheet. Hormone Health Network of The Endocrine Society. www. FS_TD_Hypothyroidism_EN-6-12. pdf. Published March 2010, 4th ed. Accessed February 25, 2013.

(10.) Cooper D, McDermott M, Wartofsky L, eds. Hyperthyroidism fact sheet. Hormone Health Network of The Endocrine Society. www. FS_TD_Hyperthyroidism_EN-web. pdf. Published March 2010, 3rd ed. Accessed February 25, 2013.

(11.) El-Hajj Fuleihan, G. Patient information: primary hyperparathyroidism (beyond the basics). UpToDate. www.uptodate. com/contents/primaryhyperparathyroidism-beyond-the-basics. Updated October 24, 2012. Accessed February 25, 2013.

(12.) Zawilska JB, Skene DJ, Arendt J. Physiology and pharmacology of melatonin in relation to biological rhythms. Pharmacol Rep. 2009;61(3):383-410.

(13.) McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/ velocardiofacial syndrome). Medicine. 2011;90(1):1-18.


* US National Library of Medicine: Medline Plus. Endocrine system. Accessed May 31, 2013.

* Hadley M, Levine J. Endocrinology. 6th ed. San Francisco, CA: Benjamin Cummings; 2006.

* Hormone Health Network. Diseases and conditions. Accessed May 31, 2013.

By Joanne M. McAndrews, PhD, (a) and Jacqueline Wu, PhD (b)

(a) Freelance Medical Writer, St. Louis, MO, and (b) owner and Medical Writer, Castle Peak Medical Writing, San Jose, CA

* Part 1: Basic Concepts and Anatomy was published in Volume 27, Number 4. These articles are based, in part, on the authors' AMWA credit workshop, "Introduction to the Endocrine System."
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Title Annotation:Science Series
Author:McAndrews, Joanne M.; Wu, Jacqueline
Publication:American Medical Writers Association Journal
Date:Jun 1, 2013
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