Hormone
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
A hormone (from Greek όρμή - "to set in motion") is a chemical messenger that carries a signal from one cell (or group of cells) to another. All multicellular organisms produce hormones (including plants).
The function of hormones is to carry information to the target cells; the action of hormones is determined by the pattern of secretion and response of the receiving tissue - the signal transduction response.
The best-known animal hormones are those produced by endocrine glands of vertebrate animals, but hormones are produced by nearly every organ system and tissue type in a multicellular organism.
Endocrine hormone molecules are secreted (released) directly into the bloodstream, while exocrine hormones (or ectohormones) are secreted directly into a duct, and from the duct they either flow into the bloodstream or they flow from cell to cell by diffusion in a process known as paracrine signalling.
Hierarchical nature of hormonal control
Hormone signaling
Hormonal signaling across this hierarchy involves the following:
- Biosynthesis of a particular hormone in a particular tissue.
- Storage and secretion of the hormone.
- Transport of the hormone to the target cell(s).
- Recognition of the hormone by an associated cell membrane or intracellular receptor protein.
- Relay and amplification of the received hormonal signal via a signal transduction process. This then leads to a cellular response. The reaction of the target cells may then be recognized by the original hormone-producing cells, leading to a down-regulation in hormone production. This is an example of a homeostatic negative feedback loop.
- Degradation of the hormone.
As can be inferred from the hierarchical diagram, hormone biosynthetic cells are typically of a specialized cell type, residing within a particular endocrine gland (e.g. the thyroid gland, ovaries or testes). Hormones may exit their cell of origin via exocytosis or another means of membrane transport. However, the hierarchical model is an over simplification of the hormonal signaling process. Typically cellular recipients of a particular hormonal signal may be one of several cell types that reside within a number of different tissues, as is the case for insulin, which triggers a diverse range of systemic physiological effects. Different tissue types may also respond differently to the same hormonal signal. Because of this, hormonal signaling is elaborate and hard to dissect.
Interactions with receptors
Most hormones initiate a cellular response by initially combining with either a specific intracellular or cell membrane associated receptor protein. A cell may have several different receptors that recognize the same hormone and activate different signal transduction pathways, or alternatively different hormones and their receptors may invoke the same biochemical pathway.
For many hormones, including most protein hormones, the receptor is membrane associated and embedded in the plasma membrane at the surface of the cell. The interaction of hormone and receptor typically triggers a cascade of secondary effects within the cytoplasm of the cell, often involving phosphorylation or dephosphorylation of various other cytoplasmic proteins, changes in ion channel permeability, or increased concentrations of intracellular molecules that may act as secondary messengers (e.g. cyclic AMP). Some protein hormones also interact with intracellular receptors located in the cytoplasm or nucleus by an intracrine mechanism.
For hormones such as steroid or thyroid hormones, their receptors are located intracellularly within the cytoplasm of their target cell. In order to bind their receptors these hormones must cross the cell membrane. The combined hormone-receptor complex then moves across the nuclear membrane into the nucleus of the cell, where it binds to specific DNA sequences, effectively amplifying or suppressing the action of certain genes, and affecting protein synthesis.[1] However, it has been shown that not all steroid receptors are located intracellularly, some are plasma membrane associated.[2]
An important consideration, dictating the level at which cellular signal transduction pathways are activated in response to a hormonal signal is the effective concentration of hormone-receptor complexes that are formed. Hormone-receptor complex concentrations are effectively determined by three factors:
- The number of hormone molecules available for complex formation
- The number of receptor molecules available for complex formation and
- The binding affinity between hormone and receptor.
The number of hormone molecules available for complex formation is usually the key factor in determining the level at which signal transduction pathways are activated. The number of hormone molecules available being determined by the concentration of circulating hormone, which is in turn influenced by the level and rate at which they are secreted by biosynthetic cells. The number of receptors at the cell surface of the receiving cell can also be varied as can the affinity between the hormone and its receptor.
Physiology of hormones
Most cells are capable of producing one or more molecules, which act as signalling molecules to other cells, altering their growth, function, or metabolism. The classical hormones produced by endocrine glands mentioned so far in this article are cellular products, specialized to serve as regulators at the overall organism level. However they may also exert their effects solely within the tissue in which they are produced and originally released.
The rate of hormone biosynthesis and secretion is often regulated by a homeostatic negative feedback control mechanism. Such a mechanism depends on factors which influence the metabolism and excretion of hormones. Thus, higher hormome concentration alone can not trigger the negative feedback mechanism. Negative feedback must be triggered by overproduction of an "effect" of the hormone.
Hormone secretion can be stimulated and inhibited by:
- Other hormones (stimulating- or releasing-hormones)
- Plasma concentrations of ions or nutrients, as well as binding globulins
- Neurons and mental activity
- Environmental changes, e.g., of light or temperature
One special group of hormones is the tropic hormones that stimulate the hormone production of other endocrine glands. For example, thyroid-stimulating hormone (TSH) causes growth and increased activity of another endocrine gland, the thyroid, which increases output of thyroid hormones.
A recently-identified class of hormones is that of the "hunger hormones" - ghrelin, orexin and PYY 3-36 - and "satiety hormones" - e.g., leptin, obestatin, nesfatin-1.
In order to release active hormones quickly into the circulation, hormone biosynthetic cells may produce and store biologically inactive hormones in the form of pre- or prohormones. These can then be quickly converted into their active hormone form in response to a particular stimulus.
Hormone effects
Hormone effects vary widely, but can include:
- stimulation or inhibition of growth,
- induction or suppression of apoptosis (programmed cell death)
- activation or inhibition of the immune system
- regulating metabolism
- preparation for a new activity (e.g., fighting, fleeing, mating)
- preparation for a new phase of life (e.g., puberty, caring for offspring, menopause)
- controlling the reproductive cycle
In many cases, one hormone may regulate the production and release of other hormones
Many of the responses to hormone signals can be described as serving to regulate metabolic activity of an organ or tissue.
Chemical classes of hormones
Vertebrate hormones fall into three chemical classes:
- Amine-derived hormones are derivatives of the amino acids tyrosine and tryptophan. Examples are catecholamines and thyroxine.
- Peptide hormones consist of chains of amino acids. Examples of small peptide hormones are TRH and vasopressin. Peptides composed of scores or hundreds of amino acids are referred to as proteins. Examples of protein hormones include insulin and growth hormone. More complex protein hormones bear carbohydrate side chains and are called glycoprotein hormones. Luteinizing hormone, follicle-stimulating hormone and thyroid-stimulating hormone are glycoprotein hormones.
- Lipid and phospholipid-derived hormones derive from lipids such as linoleic acid and arachidonic acid and phospholipids. The main classes are the steroid hormones that derive from cholesterol and the eicosanoids. Examples of steroid hormones are testosterone and cortisol. Sterol hormones such as calcitriol are a homologous system. The adrenal cortex and the gonads are primary sources of steroid hormones. Examples of eicosanoids are the widely studied prostaglandins.
Pharmacology
Many hormones and their analogues are used as medication. The most commonly-prescribed hormones are estrogens and progestagens (as methods of hormonal contraception and as HRT), thyroxine (as levothyroxine, for hypothyroidism) and steroids (for autoimmune diseases and several respiratory disorders). Insulin is used by many diabetics. Local preparations for use in otolaryngology often contain pharmacologic equivalents of adrenaline, while steroid and vitamin D creams are used extensively in dermatological practice.
A "pharmacologic dose" of a hormone is a medical usage referring to an amount of a hormone far greater than naturally occurs in a healthy body. The effects of pharmacologic doses of hormones may be different from responses to naturally-occurring amounts and may be therapeutically useful. An example is the ability of pharmacologic doses of glucocorticoid to suppress inflammation.
Important human hormones
Spelling is not uniform for many hormones. Current North American and international usage is estrogen, gonadotropin, while British usage retains the Greek diphthong in oestrogen and the unvoiced aspirant h in gonadotrophin.
Structure | Name | Abbreviation | Tissue | Cells | Mechanism | Target Tissue | Effect | |
amine - tryptophan | Melatonin (N-acetyl-5-methoxytryptamine) | pineal gland | pinealocyte | Makes you sleepy | ||||
amine - tryptophan | Serotonin | 5-HT | CNS, GI tract | enterochromaffin cell | ||||
amine - tyrosine | Thyroxine (thyroid hormone) | T4 | thyroid gland | thyroid epithelial cell | direct |
Increases metabolic rate | ||
amine - tyrosine | Triiodothyronine (thyroid hormone) | T3 | thyroid gland | thyroid epithelial cell | direct | |||
amine - tyrosine (cat) | Epinephrine (or adrenaline) | EPI | adrenal medulla | chromaffin cell | Dilates blood vessels in muscles; Increases rate of heartbeat; Raises blood glucose | |||
amine - tyrosine (cat) | Norepinephrine (or noradrenaline) | NRE | adrenal medulla | chromaffin cell | Constricts small arteries, raises blood pressure | |||
amine - tyrosine (cat) | Dopamine | DPM | hypothalamus | |||||
peptide | Antimullerian hormone (or mullerian inhibiting factor or hormone) | AMH | testes | Sertoli cell | ||||
peptide | Adiponectin | Acrp30 | adipose tissue | |||||
peptide | Adrenocorticotropic hormone (or corticotropin) | ACTH | anterior pituitary | corticotrope | cAMP | Stimulates the adrenal cortex to release hormones | ||
peptide | Angiotensinogen and angiotensin | AGT | liver | IP3 | ||||
peptide | Antidiuretic hormone (or vasopressin, arginine vasopressin) | ADH | posterior pituitary | varies | Causes kidneys to retain water | |||
peptide | Atrial-natriuretic peptide (or atriopeptin) | ANP | heart | cGMP | ||||
peptide | Calcitonin | CT | thyroid gland | parafollicular cell | cAMP | Constructs bone, decreases blood calcium level | ||
peptide | Cholecystokinin | CCK | duodenum | |||||
peptide | Corticotropin-releasing hormone | CRH | hypothalamus | cAMP | ||||
peptide | Erythropoietin | EPO | kidney | |||||
peptide | Follicle-stimulating hormone | FSH | anterior pituitary | gonadotrope | cAMP | |||
peptide | Gastrin | GRP | stomach, duodenum | G cell | Secretion of gastric juices | |||
peptide | Ghrelin | stomach | P/D1 cell | |||||
peptide | Glucagon | GCG | pancreas | alpha cells | cAMP | Breaks down glucogen, increases blood glucose level | ||
peptide | Gonadotropin-releasing hormone | GnRH | hypothalamus | IP3 | ||||
peptide | Growth hormone-releasing hormone | GHRH | hypothalamus | IP3 | Stimulates the anterior-pituitary gland to release growth hormone | |||
peptide | Human chorionic gonadotropin | hCG | placenta | syncytiotrophoblast cells | cAMP | |||
peptide | Human placental lactogen | HPL | placenta | |||||
peptide | Growth hormone | GH or hGH | anterior pituitary | somatotropes | ||||
peptide | Inhibin | testes | Sertoli cells | |||||
peptide | Insulin | INS | pancreas | beta cells | tyrosine kinase | Decreases blood glucose level | ||
peptide | Insulin-like growth factor (or somatomedin) | IGF | liver | tyrosine kinase | ||||
peptide | Leptin | LEP | adipose tissue | |||||
peptide | Luteinizing hormone | LH | anterior pituitary | gonadotropes | cAMP | Releases testosterone in males and forms corpus luteum in females | ||
peptide | Melanocyte stimulating hormone | MSH or α-MSH | anterior pituitary/pars intermedia | cAMP | ||||
peptide | Oxytocin | OXT | posterior pituitary | IP3 | Contracts the uterus and releases breast milk | |||
peptide | Parathyroid hormone | PTH | parathyroid gland | parathyroid chief cell | cAMP | Breaks down bone, increases blood calcium | ||
peptide | Prolactin | PRL | anterior pituitary | lactotrophs | Stimulates the production of breast milk | |||
peptide | Relaxin | RLN | varies | |||||
peptide | Secretin | SCT | duodenum | S cell | Stops the production of gastric juices and stimulates the pancreas to release juice | |||
peptide | Somatostatin | SRIF | hypothalamus, islets of Langerhans | delta cells | ||||
peptide | Thrombopoietin | TPO | liver, kidney | |||||
peptide | Thyroid-stimulating hormone | TSH | anterior pituitary | thyrotropes | cAMP | Stimulates the thyroid gland to release thyroid hormones | ||
peptide | Thyrotropin-releasing hormone | TRH | hypothalamus | IP3 | ||||
steroid - glu. | Cortisol | adrenal cortex (zona fasciculata) | direct | |||||
steroid - min. | Aldosterone | adrenal cortex (zona glomerulosa) | direct | Causes kidneys to retain sodium, hence water as well | ||||
steroid - sex (and) | Testosterone | testes | Leydig cells | direct | Male secondary sex features | |||
steroid - sex (and) | Dehydroepiandrosterone | DHEA | multiple | direct | ||||
steroid - sex (and) | Androstenedione | adrenal glands, gonads | direct | |||||
steroid - sex (and) | Dihydrotestosterone | DHT | multiple | direct | ||||
steroid - sex (est) | Estradiol | E2 | ovary | granulosa cells | direct | |||
steroid - sex (est) | Estrone | ovary | granulosa cells | direct | ||||
steroid - sex (est) | Estriol | placenta | syncytiotrophoblast | direct | ||||
steroid - sex (pro) | Progesterone | ovary, adrenal glands, placenta | granulosa cells | direct | ||||
sterol | Calcitriol (Vitamin D3) | skin/proximal tubule of kidneys | direct | |||||
eicosanoid | Prostaglandins | PG | seminal vesicle | |||||
eicosanoid | Leukotrienes | LT | white blood cells | |||||
eicosanoid | Prostacyclin | PGI2 | endothelium | |||||
eicosanoid | Thromboxane | TXA2 | platelets |
References
See also
- Endocrinology
- Endocrine system
- Neuroendocrinology
- Autocrine signaling
- Paracrine signaling
- Intracrine
- Cytokine
- Growth factor
- Hormone disruptor
External links
- The Hormone Foundation
- Hormones at the US National Library of Medicine Medical Subject Headings (MeSH)
- Hormones and Nutrition
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