Hormone

Epinephrine (adrenaline), a catecholamine-type hormone

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.

Hormonal signaling 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, ovaries or testes). Hormones may exit their cell of origin via exocytosis or another means of membrane transport.

Types of signalling

In animals, there are three types of signaling by extracellular, secreted molecules—endocrine, paracrine, or autocrine—based on the distance over which the signal acts.

Hormones belong to the first type: they act on target cells distant from their site of synthesis by cells of the endocrine organs. In animals, an endocrine hormone is usually carried by the blood from its site of release to the target cell.

Paracrine signaling molecules only affect target cells in close proximity (an example is the conduction of an impulse), while autocrine cells respond to substances that they themselves release.

However, the designations above are not so clear cut, as some compounds can act in two or even three types of signaling. For example, certain small peptides function both as neurotransmitters (paracrine signaling) and as hormones (endocrine signaling) that operate over longer distances. These neurohormones – definition TK.

A neurohormone is any hormone produced by neurosecretory cells, usually in the brain. Neurohormonal activity is distinguished from that of classical neurotransmitters as it can have effects on cells distant from the source of the hormone.

Neuroendocrine cells are a specialized group of nerve cells (neurons) that produce hormones. These hormones may be amines, neuropeptides, or specialized amino acids. They package the hormones in vesicles and send these packages via long processes (axons) to blood vessels. When stimulated (by hormones from the blood stream or other neurons) the neuroendocrine cells secrete the hormones into the blood stream. The hormones then travel to their target cells and may stimulate, inhibit or maintain function of these cells. The target cells may feed back information to these neurons that regulates further secretion.

Specialized groups of neuroendocrine cells can be found at the base of the third ventricle in the brain (in a region called the hypothalamus). This area controls most anterior pituitary cells and thereby regulates functions in the entire body, like responses to stress, cold, sleep, and the reproductive system. The neurons send processes to a region connecting to the pituitary stalk and the hormones (called releasing or inhibiting hormones) are released into the blood stream. They are carried by portal vessels to the pituitary cells where they may stimulate, inhibit, or maintain the function of a particular cell type. Many of the projects in the neuroendocrine group focus on the regulatory circuitry in this pathway.

The endocrine system works in close relation with the nervous system. It links the brain to the organs that control various aspects of the body. In addition, neurohormones are released by specialized groups of neurons in the brain. These function similarly to hormones and are often categorized into three major groups: catecholamines; hypothalamic neurohormones that monitor hormone release from the anterior pituitary; and hypothalamic neurohormones that monitor hormone release from the posterior pituitary. Neuroendocrinology is an area of medicine that focuses on the overlapping fields between the nervous and endocrine systems.

Overview

what goes here?

Communication usually involves six steps 1. synthesis 2. release of the sig mol by the sig cell 3. transport to target cell 4. detection of signal by a specific receptor protein 5. change in cellular metabolism or gene expression triggered by receptor-signaling complex 6. removal of the signal, often terminating the cellular response

Hormones in action

detail mechanisms

technical term for the signaling molecule (whether a hormone, neurotransmitter, or what have you) is ‘’ligand,’’ which binds to, or “fits” a site on the receptor protein, which is located on the surface of a target cell or in its nucleus or cytosol; binding causes a conformational change that initiates a sequence of reactions leading to a change in cellular function

diff cells respond differently to the same ligand, and diff receptor-ligand complexes can induce the same response in some cell types (ex of glucagons and epinephrine in liver cells, p 856)

a word on role of second messengers (intracellular signaling molecules)

Classification

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 steriod receptors are located intracellularly, some are plasma membrane associated.

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.

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.

Regulation

Hormonal regulation of some physiological activities involves a hierarchy of cell types acting on each other either to stimulate or 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 acting on input 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.

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.

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 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 cannot 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

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.

After a hormone has been secreted and has exerted its effect, its action must be terminated. This is accomplished by enzymes, which degrade, or breakdown, the hormone into metabolites. The metabolites are excreted along with bile and/or urine. Enzymes may be present in the blood or within the cell itself. Endocytosis of the receptor-hormone complex can also terminate hormone action. As noted above, the rate at which a hormone is broken down in the bloodstream is called the half life of the hormone. It is the amount of time needed to reduce the hormone concentration by one-half. This rate gives a measure of the period of time a hormone is active in the body. The endocrine system regulates hormone release and concentration through the negative feedback loop. Increases in hormone activity decrease the production and secretion of that hormone. Similarly, a decrease in activity of a hormone prompts an increase in the production and release of that hormone. The immune system as well as other factors contribute as control factors of hormone secretion. Together, these various mechanisms of control regulate the levels of hormones within the body.

Peptide hormones are made and stored in vesicles within cells until they receive a signal for secretion. Initially, peptide hormones are made as preprohormones, which are inactive, and then are converted into prohormones. These prohormones are then cut into active hormones and peptide pieces, which are all secreted together. Because of their hydrophilic (water loving) nature, peptide hormones travel freely in the blood as they dissolve. They experience short half lives and tend to bind to surface cell receptors to initiate quick cellular responses. Peptide hormones can cause the synthesis of new proteins. Steroid hormones, on the other hand, are made on demand. Because they are derived from cholesterol, they are hydrophobic (water fearing) and tend to travel in the blood with protein carriers. Consequently, they have a longer half life. Receptors for steroid hormones are traditionally found inside the target cell. Responses include the turning on and off of genes and the direct synthesis of fresh proteins. Overall, the cell responses with steroid hormones are slower than those with peptide hormones.

By rate of synthesis

Orgs must be able to respond instantly to many changes in their internal or external environment; such rapid responses are mediated primarily by peptide hormones and catecholamines; signaling cells that produce them store them in secretory vesicles just under the plasma membrane; all peptide hormones, including insulin, are synthesized as part of a longer propolypeptide, which is cleaved (def) by specific enzymes to generate the active molecule just after it is transported to a secretory vesicle. Peptide hormones mediate short responses that are terminated by their own degradation.

In contrast, steroid-producing cells, like those in the adrenal cortex, store a small supply of hormone precursor; when stim’d, converted to active hormone, which then diffuses across the cell membrane into the blood (thyroxine has a diff type of storage cell. Because cells store little of the active hormone, release takes from hours to days; transported by carrier proteins, and are not rapidly degraded; thus, responses to thyroxine and steroid hormones take awhile to occur but effects last much longer (hrs to days).

By feedback control

feedback control of hormone levels: feedback circuits, in which changes in the level of one hormone affects the levels of other hormones (esp important in coordinating the complex processes of cell growth and differentiation); ex of estrogen and progesterone?

Hormone effects

One special group of hormones is the trophic 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.

Plant hormones

Plant hormones (or plant growth regulators, or PGRs) are internally-secreted chemicals in plants that are used for regulating the plants' growth. According to a standard definition, plant hormones are signal molecules produced at specific locations, that occur in very low concentrations, and cause altered processes in target cells at other locations.

It is accepted that there are five major classes of plant hormones:

1. abscisic acid (ABA)
2. auxins
3. cytokinins(CKs)
4. ethylene
5. gibberellins (GAs)

Non-traditional plant hormones include

1. salicylic acid
2. jasmonates
3. oligosaccharins
4. brassinolides
5. small extracellular signalling peptides

• Excellent plant hormone site on the Web.

Pharmacology and cell bio research

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

[retain table?] Spelling is not uniform for many hormones. For example, 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
amine - tryptophan	Melatonin (N-acetyl-5-methoxytryptamine)		pineal gland	pinealocyte
amine - tryptophan	Serotonin	5-HT	CNS, GI tract	enterochromaffin cell
amine - tyrosine	Thyroxine (thyroid hormone)	T4	thyroid gland	thyroid epithelial cell	direct
amine - tyrosine	Triiodothyronine (thyroid hormone)	T3	thyroid gland	thyroid epithelial cell	direct
amine - tyrosine (cat)	Epinephrine (or adrenaline)	EPI	adrenal medulla	chromaffin cell
amine - tyrosine (cat)	Norepinephrine (or noradrenaline)	NRE	adrenal medulla	chromaffin cell
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
peptide	Angiotensinogen and angiotensin	AGT	liver		IP3
peptide	Antidiuretic hormone (or vasopressin, arginine vasopressin)	ADH	posterior pituitary		varies
peptide	Atrial-natriuretic peptide (or atriopeptin)	ANP	heart		cGMP
peptide	Calcitonin	CT	thyroid gland	parafollicular cell	cAMP
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
peptide	Ghrelin		stomach	P/D1 cell
peptide	Glucagon	GCG	pancreas	alpha cells	cAMP
peptide	Gonadotropin-releasing hormone	GnRH	hypothalamus		IP3
peptide	Growth hormone-releasing hormone	GHRH	hypothalamus		IP3
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
peptide	Insulin-like growth factor (or somatomedin)	IGF	liver		tyrosine kinase
peptide	Leptin	LEP	adipose tissue
peptide	Luteinizing hormone	LH	anterior pituitary	gonadotropes	cAMP
peptide	Melanocyte stimulating hormone	MSH or α-MSH	anterior pituitary/pars intermedia		cAMP
peptide	Oxytocin	OXT	posterior pituitary		IP3
peptide	Parathyroid hormone	PTH	parathyroid gland	parathyroid chief cell	cAMP
peptide	Prolactin	PRL	anterior pituitary	lactotrophs
peptide	Relaxin	RLN	varies
peptide	Secretin	SCT	duodenum	S cell
peptide	Somatostatin	SRIF	hypothalamus, islets of Langerhans	delta cells
peptide	Thrombopoietin	TPO	liver, kidney
peptide	Thyroid-stimulating hormone	TSH	anterior pituitary	thyrotropes	cAMP
peptide	Thyrotropin-releasing hormone	TRH	hypothalamus		IP3
steroid - glu.	Cortisol		adrenal cortex (zona fasciculata)		direct
steroid - min.	Aldosterone		adrenal cortex (zona glomerulosa)		direct
steroid - sex (and)	Testosterone		testes	Leydig cells	direct
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

ISBN links support NWE through referral fees

• Beato, M., Chavez, S., and M. Truss. 1996. Transcriptional regulation by steroid hormones. Steroids 61(4): 240-251. PMID 8733009
• Cooper, G. M., and R. E. Hausman. 2004. The Cell: A Molecular Approach, 3rd edition. Washington, D.C.: ASM Press & Sunderland, M.A.: Sinauer Associates. ISBN 0878932143
• Hammes, S.R. 2003. The further redefining of steroid-mediated signaling. Proc Natl Acad Sci 100(5): 2168-70 PMID 12606724
• Lodish, H., D. Baltimore, A. Berk, S. L. Zipursky, P. Matsudaira, and J. Darnell. 1995. Molecular Cell Biology, 3rd edition. New York, NY: Scientific American Books. ISBN 0716723808.
• Mathews, C.K. and K.E. van Holde. 1990. Biochemistry. San Francisco: Benjamin-Cummings. ISBN 0805350152
• Stryer, L. 1995. Biochemistry, 4th edition. New York: W.H. Freeman. ISBN 0716720094

See also

• Endocrinology
• Endocrine system
• Neuroendocrinology
• Plant hormones or plant growth regulators
• Autocrine signaling
• Paracrine signaling
• Intracrine
• Cytokine
• Growth factor
• Hormone disruptor

External links

• MeSH Hormones

• Hormone Imbalance
• Hormones and Nutrition

Hormones and endocrine glands

Hypothalamus: GnRH - TRH - CRH - GHRH - somatostatin - dopamine | Posterior pituitary: vasopressin - oxytocin | Anterior pituitary: GH - ACTH - TSH - LH - FSH - prolactin - MSH - endorphins - lipotropin Thyroid: T3 and T4 - calcitonin | Parathyroid: PTH | Adrenal medulla: epinephrine - norepinephrine | Adrenal cortex: aldosterone - cortisol - DHEA | Pancreas: glucagon- insulin - somatostatin | Ovary: estradiol - progesterone - inhibin - activin | Testis: testosterone - AMH - inhibin | Pineal gland: melatonin | Kidney: renin - EPO - calcitriol - prostaglandin | Heart atrium: ANP Stomach: gastrin | Duodenum: CCK - GIP - secretin - motilin - VIP | Ileum: enteroglucagon | Liver: IGF-1 Placenta: hCG - HPL - estrogen - progesterone Adipose tissue: leptin, adiponectin Target-derived NGF, BDNF, NT-3

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