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Adrenaline chemical structure

Epinephrine (adrenaline), a catecholamine-type 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 essentially a chemical messenger that transports a signal from one cell to another. All multicellular organisms produce hormones. 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 controlEdit

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.[1]

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.

Classes of hormonesEdit

Hormone signalingEdit

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, 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 receptorsEdit

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.[2] However, it has been shown that not all steroid receptors are located intracellularly, some are plasma membrane associated.[3]

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 hormonesEdit

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 effectsEdit

Hormone effects vary widely, but can include:

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 hormonesEdit

Vertebrate hormones fall into three chemical classes:

PharmacologyEdit

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 hormonesEdit

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.[4] and circadian homeostasis (body temperature, activity level, wakefulness) [5].

peptide Parathyroid hormone PTH parathyroid gland parathyroid chief cell cAMP increase blood Ca2+: *indirectly stimulate osteoclasts

(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 [6]
Inhibit release of insulin from beta cells [7]
Inhibit release of glucagon from alpha cells [7]
Suppress the exocrine secretory action of pancreas.

peptide Thrombopoietin TPO liver, kidney, striated muscle Myocytes megakaryocytes produce platelets[8]
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:

Protein synthesis:

  • increase hepatic production of binding proteins

Coagulation:

Increase HDL, triglyceride, height growth Decrease LDL, fat deposition Fluid balance:

Gastrointestinal tract:

  • reduce bowel motility
  • increase cholesterol in bile

Melanin:

Cancer: support hormone-sensitive breast cancers [9] Suppression of production in the body of estrogen is a treatment for these cancers.

Lung function:

Males: Prevent apoptosis of germ cells[11]

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[12]:

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[12] 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[13] Reduce spasm and relax smooth muscle (widen bronchi and regulate mucus) Antiinflammatory Reduce gall-bladder activity[14] 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 [15]
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

JournalsEdit

See alsoEdit

ReferencesEdit

  1. Mathews, CK and van Holde, K. E. (1990). "Integration and control of metabolic processes" Bowen, D. Biochemistry, 790–792, The Benjamin/Cummings publishing group.
  2. Beato M, Chavez S and Truss M (1996). Transcriptional regulation by steroid hormones. Steroids 61 (4): 240–251.
  3. Hammes SR (2003). The further redefining of steroid-mediated signaling. Proc Natl Acad Sci USA 100 (5): 21680–2170.
  4. Kosfeld M et al. (2005) Oxytocin increases trust in humans. Nature 435:673-676. PDF PMID 15931222
  5. Scientific American Mind, "Rhythm and Blues"; June/July 2007; Scientific American Mind; by Ulrich Kraft
  6. http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/otherendo/somatostatin.html Colorado State University - Biomedical Hypertextbooks - Somatostatin
  7. 7.0 7.1 Physiology at MCG 5/5ch4/s5ch4_17
  8. Kaushansky K. Lineage-specific hematopoietic growth factors. N Engl J Med 2006;354:2034-45. PMID 16687716.
  9. Hormonal Therapy
  10. Massaro D, Massaro GD (2004). Estrogen regulates pulmonary alveolar formation, loss, and regeneration in mice. American Journal of Physiology. Lung Cellular and Molecular Physiology 287 (6): L1154–9.
  11. Pentikäinen V, Erkkilä K, Suomalainen L, Parvinen M, Dunkel L. Estradiol Acts as a Germ Cell Survival Factor in the Human Testis in vitro. The Journal of Clinical Endocrinology & Metabolism 2006;85:2057-67 PMID 10843196
  12. 12.0 12.1 Placental Hormones
  13. Physiology at MCG 5/5ch9/s5ch9_13
  14. Hould F, Fried G, Fazekas A, Tremblay S, Mersereau W (1988). Progesterone receptors regulate gallbladder motility. J Surg Res 45 (6): 505–12.
  15. Diabetes-related changes in contractile responses of stomach fundus to endothelin-1 in streptozotocin-induced diabetic rats Journal of Smooth Muscle Research Vol. 41 (2005) , No. 1 35-47. Kazuki Endo1), Takayuki Matsumoto1), Tsuneo Kobayashi1), Yutaka Kasuya1) and Katsuo Kamata1)


External linksEdit


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Target-derived NGF, BDNF, NT-3

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