Hormone

Hormones (from Greek ὁρμή - "impetus") are chemicals released by cells that affect cells in other parts of the body. Only a small amount of hormone is required to alter cell metabolism. It is also a chemical messenger that transports a signal from one cell to another. All multicellular organisms produce hormones; plant hormones are also called phytohormones. Hormones in animals are often transported in the blood. Cells respond to a hormone when they express a specific receptor for that hormone. The hormone binds to the receptor protein, resulting in the activation of a signal transduction mechanism that ultimately leads to cell type-specific responses.

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

Hormonal regulation of some physiological activities involves a hierarchy of cell types acting on each other either to stimulate or to modulate the release and action of a particular hormone. The secretion of hormones from successive levels of endocrine cells is stimulated by chemical signals originating from cells higher up the hierarchical system. The master coordinator of hormonal activity in mammals is the hypothalamus, which acts on input that it receives from the central nervous system.

Other hormone secretion occurs in response to local conditions, such as the rate of secretion of parathyroid hormone by the parathyroid cells in response to fluctuations of ionized calcium levels in extracellular fluid.

Hormone signaling

Hormonal signalling across this hierarchy involves the following:

1. Biosynthesis of a particular hormone in a particular tissue
2. Storage and secretion of the hormone
3. Transport of the hormone to the target cell(s)
4. Recognition of the hormone by an associated cell membrane or intracellular receptor protein.
5. 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.
6. 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, the ovaries, or the testes). Hormones may exit their cell of origin via exocytosis or another means of membrane transport. However, the hierarchical model is an oversimplification of the hormonal signaling process. 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. However, it has been shown that not all steroid receptors are located intracellularly, some are plasma membrane associated.

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:

1. The number of hormone molecules available for complex formation
2. The number of receptor molecules available for complex formation and
3. 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 signaling molecules to other cells, altering their growth, function, or metabolism. The classical hormones produced by cells in the 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 hormone 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,
• In puberty hormones can affect mood and mind
• 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 favors the earlier spelling gonadotrophin (from trophē ‘nourishment, sustenance’ rather than tropē ‘turning, change’.

Structure	Name	Abbrev- iation	Tissue	Cells	Mechanism	Target Tissue	Effect
amine - tryptophan	Melatonin (N-acetyl-5-methoxytryptamine)		pineal gland	pinealocyte			antioxidant and causes drowsiness
amine - tryptophan	Serotonin	5-HT	CNS, GI tract	enterochromaffin cell			Controls mood, appetite, and sleep
amine - tyrosine	Thyroxine (or tetraiodothyronine) (a thyroid hormone)	T4	thyroid gland	thyroid epithelial cell	direct		less active form of thyroid hormone: increase the basal metabolic rate & sensitivity to catecholamines, affect protein synthesis
amine - tyrosine	Triiodothyronine (a thyroid hormone)	T3	thyroid gland	thyroid epithelial cell	direct		potent form of thyroid hormone: increase the basal metabolic rate & sensitivity to catecholamines, affect protein synthesis
amine - tyrosine ( cat)	Epinephrine (or adrenaline)	EPI	adrenal medulla	chromaffin cell			Fight-or-flight response: Boosts the supply of oxygen and glucose to the brain and muscles (by increasing heart rate and stroke volume, vasodilation, increasing catalysis of glycogen in liver, breakdown of lipids in fat cells. dilate the pupils Suppress non-emergency bodily processes (e.g. digestion) Suppress immune system
amine - tyrosine ( cat)	Norepinephrine (or noradrenaline)	NRE	adrenal medulla	chromaffin cell			Fight-or-flight response: Boosts the supply of oxygen and glucose to the brain and muscles (by increasing heart rate and stroke volume, vasoconstriction and increased blood pressure, breakdown of lipids in fat cells. Increase skeletal muscle readiness.
amine - tyrosine ( cat)	Dopamine (or prolactin inhibiting hormone	DPM, PIH or DA	kidney, hypothalamus	Chromaffin cells in kidney Dopamine neurons of the arcuate nucleus in hypothalamus			Increase heart rate and blood pressure Inhibit release of prolactin and TRH from anterior pituitary
peptide	Antimullerian hormone (or mullerian inhibiting factor or hormone)	AMH	testes	Sertoli cell			Inhibit release of prolactin and TRH from anterior pituitary
peptide	Adiponectin	Acrp30	adipose tissue
peptide	Adrenocorticotropic hormone (or corticotropin)	ACTH	anterior pituitary	corticotrope	cAMP		synthesis of corticosteroids ( glucocorticoids and androgens) in adrenocortical cells
peptide	Angiotensinogen and angiotensin	AGT	liver		IP3		vasoconstriction release of aldosterone from adrenal cortex dipsogen.
peptide	Antidiuretic hormone (or vasopressin, arginine vasopressin)	ADH	posterior pituitary	Parvocellular neurosecretory neurons in hypothalamus Magnocellular neurosecretory cells in posterior pituitary	varies		retention of water in kidneys moderate vasoconstriction Release ACTH in anterior pituitary
peptide	Atrial-natriuretic peptide (or atriopeptin)	ANP	heart		cGMP
peptide	Calcitonin	CT	thyroid gland	parafollicular cell	cAMP		Construct bone, reduce blood Ca2+
peptide	Cholecystokinin	CCK	duodenum				Release of digestive enzymes from pancreas Release of bile from gallbladder hunger suppressant
peptide	Corticotropin-releasing hormone	CRH	hypothalamus		cAMP		Release ACTH from anterior pituitary
peptide	Erythropoietin	EPO	kidney	Extraglomerular mesangial cells			Stimulate erythrocyte production
peptide	Follicle-stimulating hormone	FSH	anterior pituitary	gonadotrope	cAMP		In female: stimulates maturation of Graafian follicles in ovary. In male: spermatogenesis, enhances production of androgen-binding protein by the Sertoli cells of the testes
peptide	Gastrin	GRP	stomach, duodenum	G cell			Secretion of gastric acid by parietal cells
peptide	Ghrelin		stomach	P/D1 cell			Stimulate appetite, secretion of growth hormone from anterior pituitary gland
peptide	Glucagon	GCG	pancreas	alpha cells	cAMP		glycogenolysis and gluconeogenesis in liver increases blood glucose level
peptide	Gonadotropin-releasing hormone	GnRH	hypothalamus		IP3		Release of FSH and LH from anterior pituitary.
peptide	Growth hormone-releasing hormone	GHRH	hypothalamus		IP3		Release GH from anterior pituitary
peptide	Human chorionic gonadotropin	hCG	placenta	syncytiotrophoblast cells	cAMP		promote maintenance of corpus luteum during beginning of pregnancy Inhibit immune response, towards the human embryo.
peptide	Human placental lactogen	HPL	placenta				increase production of insulin and IGF-1 increase insulin resistance and carbohydrate intolerance
peptide	Growth hormone	GH or hGH	anterior pituitary	somatotropes			stimulates growth and cell reproduction Release Insulin-like growth factor 1 from liver
peptide	Inhibin		testes, ovary, fetus	Sertoli cells of testes granulosa cells of ovary trophoblasts in fetus	anterior pituitary	Inhibit production of FSH
peptide	Insulin	INS	pancreas	beta cells	tyrosine kinase		Intake of glucose, glycogenesis and glycolysis in liver and muscle from blood intake of lipids and synthesis of triglycerides in adipocytes Other anabolic effects
peptide	Insulin-like growth factor (or somatomedin)	IGF	liver	Hepatocytes	tyrosine kinase		insulin-like effects regulate cell growth and development
peptide	Leptin	LEP	adipose tissue				decrease of appetite and increase of metabolism.
peptide	Luteinizing hormone	LH	anterior pituitary	gonadotropes	cAMP		In female: ovulation In male: stimulates Leydig cell production of testosterone
peptide	Melanocyte stimulating hormone	MSH or α-MSH	anterior pituitary/ pars intermedia	Melanotroph	cAMP		melanogenesis by melanocytes in skin and hair
peptide	Orexin		hypothalamus				wakefulness and increased energy expenditure, increased appetite
peptide	Oxytocin	OXT	posterior pituitary	Magnocellular neurosecretory cells	IP3		release breast milk Contraction of cervix and vagina Involved in orgasm, trust between people. and circadian homeostasis (body temperature, activity level, wakefulness) .
peptide	Parathyroid hormone	PTH	parathyroid gland	parathyroid chief cell	cAMP		increase blood Ca2+: *indirectly stimulate osteoclasts Ca2+ reabsorption in kidney activate vitamin D (Slightly) decrease blood phosphate: (decreased reuptake in kidney but increased uptake from bones activate vitamin D)
peptide	Prolactin	PRL	anterior pituitary, uterus	lactotrophs of anterior pituitary Decidual cells of uterus			milk production in mammary glands sexual gratification after sexual acts
peptide	Relaxin	RLN	uterus	Decidual cells			Unclear in humans
peptide	Secretin	SCT	duodenum	S cell			Secretion of bicarbonate from liver, pancreas and duodenal Brunner's glands Enhances effects of cholecystokinin Stops production of gastric juice
peptide	Somatostatin	SRIF	hypothalamus, islets of Langerhans, gastrointestinal system	delta cells in islets Neuroendocrince cells of the Periventricular nucleus in hypothalamus			Inhibit release of GH and TRH from anterior pituitary Suppress release of gastrin, cholecystokinin (CCK), secretin, motilin, vasoactive intestinal peptide (VIP), gastric inhibitory polypeptide (GIP), enteroglucagon in gastrointestinal system Lowers rate of gastric emptying Reduces smooth muscle contractions and blood flow within the intestine Inhibit release of insulin from beta cells Inhibit release of glucagon from beta cells Suppress the exocrine secretory action of pancreas.
peptide	Thrombopoietin	TPO	liver, kidney, striated muscle	Myocytes		megakaryocytes	produce platelets
peptide	Thyroid-stimulating hormone (or thyrotropin)	TSH	anterior pituitary	thyrotropes	cAMP	thyroid gland	secrete thyroxine (T4) and triiodothyronine (T3)
peptide	Thyrotropin-releasing hormone	TRH	hypothalamus	Parvocellular neurosecretory neurons	IP3	anterior pituitary	Release thyroid-stimulating hormone (primarily) Stimulate prolactin release
steroid - glu.	Cortisol		adrenal cortex ( zona fasciculata and zona reticularis cells)		direct		Stimulation of gluconeogenesis Inhibition of glucose uptake in muscle and adipose tissue Mobilization of amino acids from extrahepatic tissues Stimulation of fat breakdown in adipose tissue anti-inflammatory and immunosuppressive
steroid - min.	Aldosterone		adrenal cortex ( zona glomerulosa)		direct		Increase blood volume by reabsorption of sodium in kidneys (primarily) Potassium and H+ secretion in kidney.
steroid - sex ( and)	Testosterone		testes	Leydig cells	direct		Anabolic: growth of muscle mass and strength, increased bone density, growth and strength, Virilizing: maturation of sex organs, formation of scrotum, deepening of voice, growth of beard and axillary hair.
steroid - sex ( and)	Dehydroepiandrosterone	DHEA	testes, ovary, kidney	Zona fasciculata and Zona reticularis cells of kidney theca cells of ovary Leydig cellss of testes	direct		Virilization, anabolic
steroid - sex ( and)	Androstenedione		adrenal glands, gonads		direct		Substrate for estrogen
steroid - sex ( and)	Dihydrotestosterone	DHT	multiple		direct
steroid - sex ( est)	Estradiol	E2	females: ovary, males testes	females: granulosa cells, males: Sertoli cell	direct		Females: Structural: promote formation of female secondary sex characteristics accelerate height growth accelerate metabolism (burn fat) reduce muscle mass stimulate endometrial growth increase uterine growth maintenance of blood vessels and skin reduce bone resorption, increase bone formation Protein synthesis: increase hepatic production of binding proteins Coagulation: increase circulating level of factors 2, 7, 9, 10, antithrombin III, plasminogen increase platelet adhesiveness Increase HDL, triglyceride, height growth Decrease LDL, fat deposition Fluid balance: salt (sodium) and water retention increase growth hormone increase cortisol, SHBG Gastrointestinal tract: reduce bowel motility increase cholesterol in bile Melanin: increase pheomelanin, reduce eumelanin Cancer: support hormone-sensitive breast cancers Suppression of production in the body of estrogen is a treatment for these cancers. Lung function: promote lung function by supporting alveoli. Males: Prevent apoptosis of germ cells
steroid - sex ( est)	Estrone		ovary	granulosa cells, Adipocytes	direct
steroid - sex ( est)	Estriol		placenta	syncytiotrophoblast	direct
steroid - sex ( pro)	Progesterone		ovary, adrenal glands, placenta (when pregnant)	Granulosa cells theca cells of ovary	direct		Support pregnancy: Convert endometrium to secretory stage Make cervical mucus permeable to sperm. Inhibit immune response, e.g. towards the human embryo. Decrease uterine smooth muscle contractility Inhibit lactation Inhibit onset of labor. Support fetal production of adrenal mineralo- and glucosteroids. Other: Raise epidermal growth factor-1 levels Increase core temperature during ovulation Reduce spasm and relax smooth muscle (widen bronchi and regulate mucus) Antiinflammatory Reduce gall-bladder activity Normalize blood clotting and vascular tone, zinc and copper levels, cell oxygen levels, and use of fat stores for energy. Assist in thyroid function and bone growth by osteoblasts Relsilience in bone, teeth, gums, joint, tendon, ligament and skin Healing by regulating collagen Nerve function and healing by regulating myelin Prevent endometrial cancer by regulating effects of estrogen.
sterol	Calcitriol (1,25-dihydroxyvitamin D3)		skin/ proximal tubule of kidneys		direct		Active form of vitamin D3 Increase absorption of calcium and phosphate from gastrointestinal tract and kidneys inhibit release of PTH
sterol	Calcidiol (25-hydroxyvitamin D3)		skin/ proximal tubule of kidneys		direct		Inactive form of Vitamin D3
eicosanoid	Prostaglandins	PG	seminal vesicle
eicosanoid	Leukotrienes	LT		white blood cells
eicosanoid	Prostacyclin	PGI2	endothelium
eicosanoid	Thromboxane	TXA2		platelets
	Prolactin releasing hormone	PRH	hypothalamus				Release prolactin from anterior pituitary
	Lipotropin	PRH	anterior pituitary	Corticotropes			lipolysis and steroidogenesis, stimulates melanocytes to produce melanin
	Brain natriuretic peptide	BNP	heart	Cardiac myocytes			(To a minor degree than ANP) reduce blood pressure by: reducing systemic vascular resistance, reducing blood water, sodium and fats
	Neuropeptide Y	NPY	Stomach				increased food intake and decreased physical activity
	Histamine		Stomach	ECL cells			stimulate gastric acid secretion
	Endothelin		Stomach	X cells			Smooth muscle contraction of stomach
	Pancreatic polypeptide		Pancreas	PP cells			Unknown
	Renin		Kidney	Juxtaglomerular cells			Activates the renin-angiotensin system by producing angiotensin I of angiotensinogen
	Enkephalin		Kidney	Chromaffin cells			Regulate pain