Hormones and Hormone Action | Research & Encyclopedia Articles

Hormones and Hormone Action

Hormones are biochemical messengers that regulate physiological events in living organisms. More than 100 hormones have been identified in humans. Hormones are secreted by endocrine (ductless) glands such as the hypothalamus, the pituitary gland, the pineal gland, the thyroid, the parathyroid, the thymus, the adrenals, the pancreas, the ovaries, and the testes. Hormones are secreted directly into the blood stream from where they travel to target tissues and modulate digestion, growth, maturation, reproduction, and homeostasis. The word hormone comes from the Greek word, hormon, to stir up, and indeed excitation is characteristic of the adrenaline and the sex hormones. Most hormones produce an effect on specific target tissues that are sited at some distance from the gland secreting the hormone. Although small plasma concentrations of most hormones are always present, surges in secretion trigger specific responses at one or more targets. Hormones do not fall into any one chemical category, but most are either protein molecules or steroid molecules. These biological managers keep the body systems functioning over the long term and help maintain health. The study of hormones is called endocrinology.

Hormones elicit a response at their target tissue, target organ, or target cell type through receptors. Receptors are molecular complexes that specifically recognize another molecule-in this case, a particular hormone. When the hormone is bound by its receptor, the receptor is usually altered in some way that it sends a secondary message through the cell to do something in response. Hormones that are proteins, or peptides (smaller strings of amino acids), usually bind to a receptor in the cell's outer surface and use a second messenger to relay their action. Steroid hormones such as cortisol, testosterone, and estrogen bind to receptors inside cells. Steroids are small enough to and chemically capable of passing through the cell's outer membrane. Inside the cell, these hormones bind their receptors and often enter the nucleus to elicit a response. These receptors bind DNA to regulate cellular events by controlling gene activity.

Most hormones are released into the bloodstream by a single gland. Testosterone is an exception, because it is secreted by both the adrenal glands and by the testes. Plasma concentrations of all hormones are assessed at some site that has receptors binding that hormone. The site keeps track of when the hormone level is low or high. The major area that records this information is the hypothalamus. A number of hormones are secreted by the hypothalamus that stimulate or inhibit additional secretion of other hormones at other sites. The hormones are part of a negative or positive feedback loop.

Most hormones work through a negative feedback loop. As an example, when the hypothalamus detects high levels of a hormone, it reacts to inhibit further production. And when low levels of a hormone are detected, the hypothalamus reacts to stimulate hormone production or secretion. Estrogen, however, is part of a positive feedback loop. Each month, the Graafian follicle in the ovary releases estrogen into the bloodstream as the egg develops in ever increasing amounts. When estrogen levels rise to a certain point, the pituitary secretes luteinizing hormone (LH) which triggers the egg's release of the egg into the oviduct.

The concentrations of several important biological building blocks such as amino acids are regulated by more than one hormone. For example, both calcitonin and parathyroid hormone (PTH) influence blood calcium levels directly, and other hormones affect calcium levels indirectly via other pathways.

Hormones secreted by the hypothalamus modulate other hormones. The major hormones secreted by the hypothalamus are corticotrophin releasing hormone (CRH), thyroid stimulating hormone releasing hormone (TRH), follicle stimulating hormone releasing hormone (FSHRH), luteinizing hormone releasing hormone (LRH), and growth hormone releasing hormone (GHRH). CRH targets the adrenal glands. It triggers the adrenals to release adrenocorticotropic hormone (ACTH). ACTH functions to synthesize and release corticosteroids. TRH targets the thyroid where it functions to synthesize and release the thyroid hormones T3 and T4. FSH targets the ovaries and the testes where it enables the maturation of the ovum and of spermatozoa. LRH also targets the ovaries and the testes, and its receptors are in cells that promote ovulation and increase progesterone synthesis and release. GHRH targets the anterior pituitary to release growth hormones to most body tissues, increase protein synthesis, and increase blood glucose. Hence, the hypothalamus plays a first domino role in these cascades of events.

The hypothalamus also secretes some other important hormones such as prolactin inhibiting hormone (PIH), prolactin releasing hormone (PRH), and melanocyte inhibiting hormone (MIH). PIH targets the anterior pituitary to inhibit milk production at the mammary gland, and PRH has the opposite effect. MIH targets skin pigment cells (melanocytes) to regulate pigmentation.

The pituitary has long been called the master gland because of the vast extent of its activity. It lies deep in the brain just behind the nose. The pituitary is divided into anterior and posterior regions with the anterior portion comprising about 75% of the total gland. The posterior region secretes the peptide hormones vasopressin, also called anti-diuretic hormone (ADH), and oxytocin. Both are synthesized in the hypothalamus and moved to the posterior pituitary prior to secretion. ADH targets the collecting tubules of the kidneys, increasing their permeability to water. ADH causes at the kidneys to retain water. Lack of ADH leads to a condition called diabetes insipidus characterized by excessive urination. Oxytocin targets the uterus and the mammary glands in the breasts. Oxytocin begins labor prior to birth and also functions in the ejection of milk. The drug, pitocin, is a synthetic form of oxytocin and is used medically to induce labor.

The anterior pituitary (AP) secretes a number of hormones. The cells of the AP are classified into five types based on what they secrete. These cells are somatotrophs, corticotrophins, thyrotrophs, lactotrophs, and gonadotrophs. Respectively, they secrete growth hormone (GH), ACTH, TSH, prolactin, and LH and FSH. Each of these hormones is either a polypeptide or a glycoprotein. GH controls cellular growth, protein synthesis, and elevation of blood glucose concentration. ACTH controls secretion of some hormones by the adrenal cortex (mainly cortisol). TSH controls thyroid hormone secretion in the thyroid. In males, prolactin enhances testosterone production; in females, it initiates and maintains LH to promote milk secretion from the mammary glands. In females, FSH initiates ova development and induces ovarian estrogen secretion. In males, FSH stimulates sperm production in the testes. LH stimulates ovulation and formation of the corpus luteum, which produces progesterone. In males, LH stimulates interstitial cells to produce testosterone. Each AP hormone is secreted in response to a hypothalamic releasing hormone.

The thyroid lies under the larynx and synthesizes two hormones, thyroxine and tri-iodothyronine. This gland takes up iodine from the blood and has the highest iodine level in the body. The iodine is incorporated into the thyroid hormones. Thyroxine has four iodine atoms and is called T4. Tri-iodothyronine has three iodine atoms and is called T3. Both T3 and T4 function to increase the metabolic rate of several cells and tissues. The brain, testes, lungs, and spleen are not affected by thyroid hormones, however. T3 and T4 indirectly increase blood glucose levels as well as the insulin-promoted uptake of glucose by fat cells. Their release is modulated by TSH-RH from the hypothalamus. TSH secretion increases in cold infants. When temperature drops, a metabolic increase is triggered by TSH. Chronic stress seems to reduce TSH secretion which, in turn, decreases T3 and T4 output.

The parathyroid glands are attached to the bottom of the thyroid gland. They secrete the polypeptide parathyroid hormone (PTH), which plays a crucial role in monitoring blood calcium and phosphate levels. About 99% of the body's calcium is in the bones, and 85% of the magnesium is also found in bone. Low blood levels of calcium stimulate PTH release into the bloodstream in two steps. Initially, calcium is released from the fluid around bone cells. And later, calcium can be drawn from bone itself. Although, only about 1% of bone calcium is readily exchangeable. PTH can also increase the absorption of calcium in the intestines by stimulating the kidneys to produce a vitamin D-like substance that facilitates this action. High blood calcium levels will inhibit PTH action, and magnesium (which is chemically similar to calcium) shows a similar effect.

The two adrenal glands, one on top of each kidney, each have two distinct regions. The outer region (the medulla) produces adrenaline and noradrenaline and is under the control of the sympathetic nervous system. The inner region (the cortex) produces a number of steroid hormones. The cortical steroid hormones include mineralocorticoids (mainly aldosterone), glucocorticoids (mainly cortisol), and gonadocorticoids. These steroids are derived from cholesterol. Although cholesterol receives a lot of bad press, some of it is necessary. Steroid hormones act by regulating gene expression, hence, their presence controls the production of numerous factors with multiple roles. Aldosterone and cortisol are the major human steroids in the cortex. However, testosterone and estrogen are secreted by adults (both male and female) at very low levels.

Aldosterone plays an important role in regulating body fluids. It increases blood levels of sodium and water and lowers blood potassium levels. Low blood sodium levels trigger aldosterone secretion via the renin-angiotensin pathway. Renin is produced by the kidney, and angiotensin originates in the liver. High blood potassium levels also trigger aldosterone release. ACTH has a minor promoting effect on aldosterone. Aldosterone targets the kidney where it promotes sodium uptake and potassium excretion. Since sodium ions influence water retention, the result is a net increase in body fluid volume.

Blood cortisol levels fluctuate dramatically throughout the day and generally peak in the early morning. Presumably, this early peak enables humans to face the varied daily stressors they encounter. Cortisol secretion is stimulated by physical trauma, cold, burns, heavy exercise, and anxiety. Cortisol targets the liver, skeletal muscle, and adipose tissue. Its overall effect is to provide amino acids and glucose to meet synthesis and energy requirements for normal metabolism and during periods of stress. Because of its anti-inflammatory action, it is used clinically to reduce swelling.

The adrenal medullary hormones are epinephrine (adrenaline) and nor-epinephrine (nor-adrenaline). Both of these hormones serve to supplement and prolong the fight or flight response initiated in the nervous system. This response includes the neural effects of increased heart rate, peripheral blood vessel constriction, sweating, spleen contraction, glycogen conversion to glucose, dilation of bronchial tubes, decreased digestive activity, and lowered urine output.

The condition of stress presents a model for reviewing one way that multiple systems and hormones interact. During stress, the nervous, endocrine, digestive, urinary, respiratory, circulatory, and immune response are all tied together. For example, the hypothalamus sends nervous impulses to the spinal cord to stimulate the fight or flight response and releases CRH that promotes ACTH secretion by the pituitary. ACTH, in turn, triggers interleukins to respond which promote immune cell functions. ACTH also stimulates cortisol release at the adrenal cortex that helps buffer the person against stress. As part of a negative feedback loop, ACTH and cortisol receptors on the hypothalamus assess when sufficient levels of these hormones are present and then inhibit their further release. De-stressing occurs over a period of time after the stressor is gone. The systems eventually return to normal.

The pancreas folds under the stomach, secretes the hormones insulin, glucagon, and somatostatin. About 70% of the pancreatic hormone-secreting cells are called beta cells and secrete insulin; another 22%, or so, are called alpha cells and secrete glucagon. The remaining gamma cells secrete somatostatin, also known as growth hormone inhibiting hormone (GHIH). The alpha, beta, and gamma cells comprise the islets of Langerhans which are scattered throughout the pancreas.

Insulin and glucagon have reciprocal roles. Insulin promotes the storage of glucose, fatty acids, and amino acids, whereas, glucagon stimulates mobilization of these constituents from storage into the blood. Both are relatively short polypeptides. Insulin release is triggered by high blood glucose levels. It lowers blood sugar levels by binding a cell surface receptor and accelerating glucose transport into the cell where glucose is converted into glycogen. Insulin also inhibits the release of glucose by the liver in order to keep blood levels down. Increased blood levels of GH and ACTH also stimulate insulin secretion. Not all cells require insulin to store glucose, however. Brain, liver, kidney, intestinal, epithelium, and the pancreatic islets can take up glucose independently of insulin. Insulin excess can cause hypoglycemia leading to convulsions or coma, and insufficient levels of insulin can cause diabetes mellitus, which can be fatal if left untreated. Diabetes mellitus is the most common endocrine disorder.

The female reproductive hormones arise from the hypothalamus, the anterior pituitary, and the ovaries. Although detectable amounts of the steroid hormone estrogen are present during fetal development, at puberty estrogen levels rise to initiate secondary sexual characteristics. Gonadotropin releasing hormone (GRH) is released by the hypothalamus to stimulate pituitary release of LH and FSH. LH and FSH propagate egg development in the ovaries. Eggs (ova) exist at various stages of development, and the maturation of one ovum takes about 28 days and is called the ovarian or menstrual cycle. The ova are contained within follicles, which are support organs for ova maturation. About 450 of a female's 150,000 germ cells mature to leave the ovary. The hormones secreted by the ovary include estrogen, progesterone, and small amounts of testosterone.

As an ovum matures, rising estrogen levels stimulate additional LH and FSH release from the pituitary. Prior to ovulation, estrogen levels drop, and LH and FSH surge to cause the ovum to be released into the fallopian tube. The cells of the burst follicle begin to secrete progesterone and some estrogen. These hormones trigger thickening of the uterine lining, the endometrium, to prepare it for implantation should fertilization occur. The high progesterone and estrogen levels prevent LH and FSH from further secretion-thus hindering another ovum from developing. If fertilization does not occur, eight days after ovulation the endometrium deteriorates resulting in menstruation. The falling estrogen and progesterone levels which follow trigger LH and FSH, starting the cycle all over again.

Although estrogen and progesterone have major roles in the menstrual cycle, these hormones have receptors on a number of other body tissues. Estrogen has a protective effect on bone loss, which can lead to osteoporosis. And progesterone, which is a competitor for androgen sites, blocks actions that would result from testosterone activation. Estrogen receptors have even been found in the forebrain indicating a role in female neuronal function or development.

Hormones related to pregnancy include human chorionic gonadotrophin (HCG), estrogen, human chorionic somatomammotrophin (HCS), and relaxin. HCG is released by the early embryo to signal implantation. Estrogen and HCS are secreted by the placenta. And relaxin is secreted by the ovaries as birth nears to relax the pelvic area in preparation for labor.

Male reproductive hormones come from the hypothalamus, the anterior pituitary, and the testes. As in females, GRH is released from the hypothalamus, which stimulates LH and FSH release from the pituitary. In males, LH and FSH facilitate spermatogenesis. The steroid hormone testosterone is secreted from the testes and can be detected in early embryonic development up until shortly after birth. Testosterone levels are quite low until puberty. At puberty, rising levels of testosterone stimulate male reproductive development including secondary characteristics.

LH stimulates testosterone release from the testes. FSH promotes early spermatogenesis, whereas testosterone is required to complete spermatogenic maturation to facilitate fertilization. In addition to testosterone, LH, and FSH, the male also secretes prostaglandins. These substances promote uterine contractions that help propel sperm towards an egg in the fallopian tubes during sexual intercourse. Prostaglandins are produced in the seminal vesicles, and are not classified as hormones by all authorities.

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