Hormone
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Revision as of 03:38, 11 September 2008
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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.
Chemical classes of hormones Amine hormones: norepinephrine and triiodothryonine Amine hormones: norepinephrine and triiodothryonine Steroid hormones: cortisol and vitamin D3 Steroid hormones: cortisol and vitamin D3
Griffin and Ojeda identify three different classes of hormone based on their chemical composition:
Amines
Amines, such as norepinephrine, epinephrine, and dopamine, are derived from single amino acids, in this case tyrosine. Thyroid hormones such as 3,5,3’-triiodothyronine (T3) and 3,5,3’,5’-tetraiodothyronine (thyroxine, T4) make up a subset of this class because they derive from the combination of two iodinated tyrosine amino acid residues.
Peptide and protein
Peptide hormones and protein hormones consist of three (in the case of thyrotropin-releasing hormone) to more than 200 (in the case of follicle-stimulating hormone) amino acid residues and can have molecular weights as large as 30,000. All hormones secreted by the pituitary gland are peptide hormones, as are leptin from adipocytes, ghrelin from the stomach, and insulin from the pancreas.
Steroid
Steroid hormones are converted from their parent compound, cholesterol. Mammalian steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestagens.
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.
Endocrine System
The endocrine system is an integrated system of small organs that involve the release of extracellular signaling molecules known as hormones. The endocrine system is instrumental in regulating metabolism, growth, development and puberty, tissue function, and also plays a part in determining mood. The field of medicine that deals with disorders of endocrine glands is endocrinology, a branch of the wider field of internal medicine.
Function of endocrine organs, hormones and receptors
Hormones are molecules that act as signals from one type of cells to another. Most hormones reach their targets via the blood.
All multicellular organisms need coordinating systems to regulate and integrate the function of cells. Two mechanisms perform this function in higher animals: the nervous system and the endocrine system. The endocrine system acts through the release (generally into the blood) of chemical agents and is vital to the proper development and function of organisms. As Hadley notes, the integration of developmental events such as proliferation, growth, and differentiation (including histogenesis and organogenesis) and the coordination of metabolism, respiration, excretion, movement, reproduction, and sensory perception depend on chemical cues, substances synthesised and secreted by specialised cells.
Endocrinology is concerned with the study of the biosynthesis, storage, chemistry, and physiological function of hormones and with the cells of the endocrine glands and tissues that secrete them.
The endocrine system consists of several glands, in different parts of the body, that secrete hormones directly into the blood rather than into a duct system. Hormones have many different functions and modes of action; one hormone may have several effects on different target organs, and, conversely, one target organ may be affected by more than one hormone.
In the original 1902 definition by Bayliss and Starling (see below), they specified that, to be classified as a hormone, a chemical must be produced by an organ, be released (in small amounts) into the blood, and be transported by the blood to a distant organ to exert its specific function. This definition holds for most "classical" hormones, but there are also paracrine mechanisms (chemical communication between cells within a tissue or organ), autocrine signals (a chemical that acts on the same cell), and intracrine signals (a chemical that acts within the same cell). A neuroendocrine signal is a "classical" hormone that is released into the blood by a neurosecretory neuron (see article on Neuroendocrinology).
Hormones act by binding to specific receptors in the target organ. As Baulieu notes, a receptor has at least two basic constituents:
- a recognition site, to which the hormone binds
- an effector site, which precipitates the modification of cellular function.
Between these is a "transduction mechanism" in which hormone binding induces allosteric modification that, in turn, produces the appropriate response.
Function
The Endocrine system is an information signal system much like the nervous system. However, the nervous system uses nerves to conduct information, whereas the endocrine system mainly uses blood vessels as information channels. Glands located in many regions of the body release into the bloodstream specific chemical messengers called hormones. Hormones regulate the many and varied functions of an organism, e.g., mood, growth and development, tissue function, and metabolism, as well as sending messages and acting on them.
Types of signaling
The typical mode of cell signaling in the endocrine system is endocrine signaling. However, there are also other modes, i.e., paracrine, autocrine, and neuroendocrine signaling. Purely neurocrine signaling between neurons, on the other hand, belongs completely to the nervous system.
Endocrine
A number of glands that signal each other in sequence is usually referred to as an axis, for example the Hypothalamic-pituitary-adrenal axis.
Typical endocrine glands are the pituitary, thyroid, and adrenal glands. Features of endocrine glands are, in general, their ductless nature, their vascularity, and usually the presence of intracellular vacuoles or granules storing their hormones. In contrast exocrine glands such as salivary glands, sweat glands, and glands within the gastrointestinal tract tend to be much less vascular and have ducts or a hollow lumen.
Autocrine
Other signaling can target the same cell.
Paracrine
Paracrine signaling is where the target cell is nearby.
Juxtacrine
Juxtacrine signals are transmitted along cell membranes via protein or lipid components integral to the membrane and are capable of affecting either the emitting cell or cells immediately adjacent.
Role in disease
Diseases of the endocrine system are common,including diseases such as diabetes mellitus, thyroid disease, and obesity. Endocrine disease is characterised by dysregulated hormone release (a productive Pituitary adenoma), inappropriate response to signalling (Hypothyroidism), lack or destruction of a gland (Diabetes mellitus type 1, diminished erythropoiesis in Chronic renal failure), or structural enlargement in a critical site such as the neck (Toxic multinodular goitre). Hypofunction of endocrine glands can occur as result of loss of reserve, hyposecretion, agenesis, atrophy, or active destruction. Hyperfunction can occur as result of hypersecretion, loss of suppression, hyperplastic, or neoplastic change, or hyperstimulation.
Endocrinopathies are classified as primary, secondary, or tertiary. Primary endocrine disease inhibits the action of downstream glands. Tertiary endocrine disease is associated with dysfunction of the hypothalamus and its releasing hormones.
Cancer can occur in endocrine glands, such as the thyroid, and hormones have been implicated in signalling distant tissues to proliferate, for example the Estrogen receptor has been shown to be involved in certain breast cancers. Endocrine, Paracrine, and autocrine signalling have all been implicated in proliferation, one of the required steps of oncogenesis.
Hypothalamus
| Secreted Hormone | Abbreviation | From Cells | Effects |
|---|---|---|---|
| Tyrotropin releasing hormone | TRH | parvocellular Neurosecretory neurons | Release Thyroid stimulatory hormone from Anterior pitutory |
| Gonadotropin-releasing hormone | GnRH | Neuroendocine cells of the Preoptic area | Release of FSH and LH from anterior pituitary. |
| Growth hormone-releasing hormone | GHRH | Neuroendocrine neurons of the Arcuate nucleus | Release GH from anterior pituitary |
| Corticotropin-releasing hormone | CRH | Parvocellular neurosecretory neurons | Release ACTH from anterior pituitary |
| Oxytocin | Magnocellular neurosecretory cells | Contraction of cervix and vagina
Involved in orgasm, trust between people; and circadian homeostasis (body temperature, activity level, wakefulness); release breast milk | |
| Vasopressin | Parvocellular neurosecretory neurons | Increases permeability of distal convoluted tubule and collecting duct to water in the nephrons of the kidney, thus increasing water reabsorbiton. | |
| Somatostatin, also growth hormone-inhibiting hormone | SS or GHIH | Neuroendocrince cells of the Periventricular nucleus | Inhibit release of GH and TSH from anterior pituitary |
| Prolactin inhibiting hormone or Dopamine | PIH or DA | Dopamine neurons of the arcuate nucleus | Inhibit release of prolactin and TSH from anterior pituitary |
| Prolactin-releasing hormone | PRH | Release prolactin from anterior pituitary |
Pineal Body
| Secreted Hormone | Abbreviation | From Cells | Effects |
|---|---|---|---|
| Melatonin (Primarily) | Pinealocytes | antioxidant and causes drowsiness |
Pitutory Gland (hypophysis) : Anterior Pituitary lobe
| Secreted Hormone | Abbreviation | From Cells | Effects |
|---|---|---|---|
| Growth hormone | GH | Somatotropes | stimulates growth and cell reproduction
Release Insulin-like growth factor 1 from liver |
| Prolactin | PRL | Lactotropes | milk production in mammary glands
sexual gratification after sexual acts |
| Adrenocorticotropic hormone or corticotropin | ACTH | Corticotropes | synthesis of corticosteroids (glucocorticoids and androgens) in adrenocortical cells |
| Lipotropin | Corticotropes | lipolysis and steroidogenesis,
stimulates melanocytes to produce melanin | |
| Thyroid-stimulating hormone or thyrotropin | TSH | Thyrotropes | stimulates thyroid gland to secrete thyroxine (T4) and triiodothyronine (T3) |
| Follicle-stimulating hormone | FSH | Gonadotropes | 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 |
| Luteinizing hormone | LH | Gonadotropes | In female: ovulation
In male: stimulates Leydig cell production of testosterone |
