Adrenocorticotropic hormone - wikipedia Adrenocorticotropic hormone This article is about adrenocorticotropic hormone as a natural hormone. For adrenocorticotropic hormone as a medication and diagnostic agent, see Adrenocorticotropic hormone ( medication ). pro-opiomelanocortin Identifiers Symbol OMC Entrez 5443 HUGO 9201 OMIM 176830 RefSeq NM_000939 UniProt P01189 Other data Locus Chr. 2 p23 Adrenocorticotropic hormone ( ACTH, also adrenocorticotropin, corticotropin ) is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic - pituitary - adrenal axis and is often produced in response to biological stress ( along with its precursor corticotropin - releasing hormone from the hypothalamus ). Its principal effects are increased production and release of cortisol by the cortex of the adrenal gland. ACTH is also related to the circadian rhythm in many organisms. Deficiency of ACTH is a sign of secondary adrenal insufficiency ( suppressed production of ACTH due to an impairment of the pituitary gland or hypothalamus, cf. hypopituitarism ) or tertiary adrenal insufficiency ( disease of the hypothalamus, with a decrease in the release of corticotropin releasing hormone CRH ). Conversely, chronically elevated ACTH levels occur in primary adrenal insufficiency ( e.g. Addison 's disease ) when adrenal gland production of cortisol is chronically deficient. In Cushing 's disease a pituitary tumor is the cause of elevated ACTH ( from the anterior pituitary ) and an excess of cortisol ( hypercortisolism ) -- this constellation of signs and symptoms is known as Cushing 's syndrome. Contents 1 Production and regulation 2 Structure 3 Function 4 ACTH receptors outside the adrenal gland 5 Synthetic ACTH 6 Discovery 7 Associated conditions 8 See also 9 References 10 External links Production and regulation POMC, ACTH and β - lipotropin are secreted from corticotropes in the anterior lobe ( or adenohypophysis ) of the pituitary gland in response to the hormone corticotropin - releasing hormone ( CRH ) released by the hypothalamus. ACTH is synthesized from pre-pro - opiomelanocortin ( pre-POMC ). The removal of the signal peptide during translation produces the 241 - amino acid polypeptide POMC, which undergoes a series of post-translational modifications such as phosphorylation and glycosylation before it is proteolytically cleaved by endopeptidases to yield various polypeptide fragments with varying physiological activity. These fragments include : polypeptide fragment alias abbreviation amino acid residues NPP 27 -- 102 melanotropin gamma γ - MSH 77 -- 87 potential peptide 105 -- 134 corticotropin adrenocorticotropic hormone ACTH 138 -- 176 melanotropin alpha melanocyte - stimulating hormone α - MSH 138 -- 150 corticotropin - like intermediate peptide CLIP 156 -- 176 lipotropin beta β - LPH 179 -- 267 lipotropin gamma γ - LPH 179 -- 234 melanotropin beta β - MSH 217 -- 234 beta - endorphin 237 -- 267 met - enkephalin 237 -- 241 In order to regulate the secretion of ACTH, many substances secreted within this axis exhibit slow / intermediate and fast feedback - loop activity. Glucocorticoids secreted from the adrenal cortex work to inhibit CRH secretion by the hypothalamus, which in turn decreases anterior pituitary secretion of ACTH. Glucocorticoids may also inhibit the rates of POMC gene transcription and peptide synthesis. The latter is an example of a slow feedback loop, which works on the order of hours to days, whereas the former works on the order of minutes. The half - life of ACTH in human blood is about ten minutes. Structure ACTH consists of 39 amino acids, the first 13 of which ( counting from the N - terminus ) may be cleaved to form α - melanocyte - stimulating hormone ( α - MSH ). ( This common structure is responsible for excessively tanned skin in Addison 's disease. ) After a short period of time, ACTH is cleaved into α - melanocyte - stimulating hormone ( α - MSH ) and CLIP, a peptide with unknown activity in humans. Human ACTH has a molecular weight of 4,540 atomic mass units ( Da ). Function ACTH stimulates secretion of glucocorticoid steroid hormones from adrenal cortex cells, especially in the zona fasciculata of the adrenal glands. ACTH acts by binding to cell surface ACTH receptors, which are located primarily on adrenocortical cells of the adrenal cortex. The ACTH receptor is a seven - membrane - spanning G protein - coupled receptor. Upon ligand binding, the receptor undergoes conformation changes that stimulate the enzyme adenylyl cyclase, which leads to an increase in intracellular cAMP and subsequent activation of protein kinase A. ACTH influences steroid hormone secretion by both rapid short - term mechanisms that take place within minutes and slower long - term actions. The rapid actions of ACTH include stimulation of cholesterol delivery to the mitochondria where the P450scc enzyme is located. P450scc catalyzes the first step of steroidogenesis that is cleavage of the side - chain of cholesterol. ACTH also stimulates lipoprotein uptake into cortical cells. This increases the bioavailability of cholesterol in the cells of the adrenal cortex. The long term actions of ACTH include stimulation of the transcription of the genes coding for steroidogenic enzymes, especially P450scc, steroid 11β - hydroxylase, and their associated electron transfer proteins. This effect is observed over several hours. In addition to steroidogenic enzymes, ACTH also enhances transcription of mitochondrial genes that encode for subunits of mitochondrial oxidative phosphorylation systems. These actions are probably necessary to supply the enhanced energy needs of adrenocortical cells stimulated by ACTH. Reference ranges for blood tests, showing adrenocorticotropic hormone ( green at left ) among the hormones with smallest concentration in the blood. ACTH receptors outside the adrenal gland As indicated above, ACTH is a cleavage product of the pro-hormone, proopiomelanocortin ( POMC ), which also produces other hormones including α - MSH that stimulates the production of melanin. A family of related receptors mediates the actions of these hormones, the MCR, or melanocortin receptor family. These are mainly not associated with the pituitary - adrenal axis. MC2R is the ACTH receptor. While it has a crucial function in regulating the adrenal, it is also expressed elsewhere in the body, specifically in the osteoblast, which is responsible for making new bone, a continual and highly regulated process in the bodies of air - breathing vertebrates. The functional expression of MC2R on the osteoblast was discovered by Isales et alia in 2005. Since that time, it has been demonstrated that the response of bone forming cells to ACTH includes production of VEGF, as it does in the adrenal. This response might be important in maintaining osteoblast survival under some conditions. If this is physiologically important, it probably functions in conditions with short - period or intermittent ACTH signaling, since with continual exposure of osteoblasts to ACTH, the effect was lost in a few hours. Synthetic ACTH An active synthetic form of ACTH, consisting of the first 24 amino acids of native ACTH, was first synthesized by Klaus Hofmann at the University of Pittsburgh. Discovery While working on her dissertation, Evelyn M. Anderson co-discovered ACTH with James Bertram Collip and David Landsborough Thomson and, in a paper published in 1933, explained its function in the body. Associated conditions Diseases of the pituitary, the gland that produces, among others, the hormone ACTH Hypopituitarism, the hyposecretion of ACTH in the pituitary, leading to secondary adrenal insufficiency ( a form of hypocorticism ) Addison 's disease, the primary adrenal insufficiency ( another form of hypocorticism ) Cushing 's syndrome, hypercorticism, one of the causes is hypersecretion of ACTH Small cell carcinoma, a common cause of ACTH secreted ectopically Congenital adrenal hyperplasia, diseases in the production of cortisol Nelson 's syndrome, the rapid enlargement of the ACTH producing pituitary after the removal of both adrenal glands Adrenoleukodystrophy, can be accompanied by adrenal insufficiency West syndrome ( `` infantile spasms '' ), a disease where ACTH is used as a therapy Postorgasmic illness syndrome ( POIS ), through production of tyrosine hydroxylase and dopamine β - hydroxylase, which two enzymes comprise the biochemical mechanism by which norepinephrine and epinephrine are produced. See also Corticorelin Dexamethasone suppression test References Jump up ^ I.K. Morton ; Judith M. Hall ( December 6, 2012 ). Concise Dictionary of Pharmacological Agents : Properties and Synonyms. Springer Science & Business Media. pp. 84 --. ISBN 978 - 94 - 011 - 4439 - 1. Jump up ^ Dibner C, Schibler U, Albrecht U ( 2010 ). `` The mammalian circadian timing system : organization and coordination of central and peripheral clocks ''. Annual Review of Physiology. 72 : 517 -- 49. doi : 10.1146 / annurev - physiol - 021909 - 135821. PMID 20148687 Jump up ^ `` Adrenocorticotropic Hormone ( ACTH ) ''. Jump up ^ `` Pro-opiomelocortin precursor ''. Retrieved April 8, 2013. Jump up ^ Yalow RS, Glick SM, Roth J, Berson SA ( November 1964 ). `` Radioimmunoassay of human plasma acth ''. The Journal of Clinical Endocrinology and Metabolism. 24 ( 11 ) : 1219 -- 25. doi : 10.1210 / jcem - 24 - 11 - 1219. PMID 14230021. Jump up ^ PROOPIOMELANOCORTIN ; NCBI -- > POMC Retrieved on September 28, 2009 Jump up ^ Raikhinstein M, Zohar M, Hanukoglu I ( February 1994 ). `` cDNA cloning and sequence analysis of the bovine adrenocorticotropic hormone ( ACTH ) receptor ''. Biochimica et Biophysica Acta. 1220 ( 3 ) : 329 -- 32. doi : 10.1016 / 0167 - 4889 ( 94 ) 90157 - 0. PMID 8305507. ^ Jump up to : Hanukoglu I, Feuchtwanger R, Hanukoglu A ( November 1990 ). `` Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells '' ( PDF ). The Journal of Biological Chemistry. 265 ( 33 ) : 20602 -- 8. PMID 2173715. ^ Jump up to : Raikhinstein M, Hanukoglu I ( November 1993 ). `` Mitochondrial - genome - encoded RNAs : differential regulation by corticotropin in bovine adrenocortical cells ''. Proceedings of the National Academy of Sciences of the United States of America. 90 ( 22 ) : 10509 -- 13. Bibcode : 1993PNAS... 9010509R. doi : 10.1073 / pnas. 90.22. 10509. PMC 47806. PMID 7504267. Jump up ^ Isales CM, Zaidi M, Blair HC ( March 2010 ). `` ACTH is a novel regulator of bone mass ''. Annals of the New York Academy of Sciences. 1192 : 110 -- 6. Bibcode : 2010NYASA1192... 110I. doi : 10.1111 / j. 1749 - 6632.2009. 05231. x. PMID 20392225. Jump up ^ Zhong Q, Sridhar S, Ruan L, Ding KH, Xie D, Insogna K, Kang B, Xu J, Bollag RJ, Isales CM ( May 2005 ). `` Multiple melanocortin receptors are expressed in bone cells ''. Bone. 36 ( 5 ) : 820 -- 31. doi : 10.1016 / j. bone. 2005.01. 020. PMID 15804492. Jump up ^ Zaidi M, Sun L, Robinson LJ, Tourkova IL, Liu L, Wang Y, Zhu LL, Liu X, Li J, Peng Y, Yang G, Shi X, Levine A, Iqbal J, Yaroslavskiy BB, Isales C, Blair HC ( May 2010 ). `` ACTH protects against glucocorticoid - induced osteonecrosis of bone ''. Proceedings of the National Academy of Sciences of the United States of America. 107 ( 19 ) : 8782 -- 7. Bibcode : 2010PNAS... 107.8782 Z. doi : 10.1073 / pnas. 0912176107. PMC 2889316. PMID 20421485. Jump up ^ `` Simulated ACTH ''. Time. December 12, 1960. Jump up ^ Johstone, Rose ( 2003 ). `` A Sixty - Year Evolution of Biochemistry at McGill University '' ( PDF ). Scientia Canadensis. 27 : 27 -- 83. doi : 10.7202 / 800458ar. Jump up ^ James B. Collip, Evelyn Anderson, D.L. Thomson ( August 12, 1933 ). `` The adrenotropic hormone of the anterior pituitary lobe ''. Lancet. 222 ( 5737 ) : 347 -- 348. doi : 10.1016 / S0140 - 6736 ( 00 ) 44463 - 6. CS1 maint : Uses authors parameter ( link ) External links Adrenocorticotropic Hormone at the US National Library of Medicine Medical Subject Headings ( MeSH ) Hormones Endocrine glands Hypothalamic - pituitary Hypothalamus GnRH TRH Dopamine CRH GHRH Somatostatin ( GHIH ) MCH Posterior pituitary Oxytocin Vasopressin Anterior pituitary FSH LH TSH Prolactin POMC CLIP ACTH MSH Endorphins Lipotropin GH Adrenal axis Adrenal cortex aldosterone cortisol cortisone DHEA DHEA - S androstenedione Adrenal medulla epinephrine norepinephrine Thyroid Thyroid hormone Calcitonin Thyroid axis Parathyroid PTH Gonadal axis Testis testosterone AMH inhibin Ovary estradiol progesterone activin and inhibin relaxin Placenta hCG HPL estrogen progesterone Pancreas glucagon insulin amylin somatostatin pancreatic polypeptide Pineal gland melatonin N, N - dimethyltryptamine 5 - methoxy - N, N - dimethyltryptamine Other Thymus Thymosins Thymosin α1 Beta thymosins Thymopoietin Thymulin Digestive system Stomach gastrin ghrelin Duodenum CCK Incretins GIP GLP - 1 secretin motilin VIP Ileum enteroglucagon peptide YY Liver / other Insulin - like growth factor IGF - 1 IGF - 2 Adipose tissue leptin adiponectin resistin Skeleton Osteocalcin Kidney renin EPO calcitriol prostaglandin Heart Natriuretic peptide ANP BNP Peptides : neuropeptides Hormones see hormones Opioid peptides Dynorphins Dynorphin A Dynorphin A Dynorphin B Big dynorphin Leumorphin α - Neoendorphin β - Neoendorphin Endomorphins Endomorphin - 1 Endomorphin - 2 Endorphins α - Endorphin β - Endorphin γ - Endorphin Enkephalins Met - enkephalin Leu - enkephalin Others Adrenorphin Amidorphin Hemorphin Hemorphin - 4 Nociceptin Opiorphin Spinorphin Valorphin Other neuropeptides Kinins Bradykinins Tachykinins : mammal Substance P Neurokinin A Neurokinin B amphibian Kassinin Physalaemin Neuromedins U Orexins Other Angiotensin Bombesin Calcitonin gene - related peptide Carnosine Cocaine - and amphetamine - regulated transcript Delta sleep - inducing peptide FMRFamide Galanin Galanin - like peptide Gastrin releasing peptide Ghrelin Neuropeptide AF Neuropeptide FF Neuropeptide SF Neuropeptide VF Neuropeptide S Neuropeptide Y Neurophysins Neurotensin Pancreatic polypeptide Pituitary adenylate cyclase activating peptide RVD - Hpα VGF Appetite stimulants ( A15 ) Exogenous Amitriptyline Clonidine Cyproheptadine Dexamethasone Dronabinol / Tetrahydrocannabinol ( Cannabis ) Medroxyprogesterone acetate Megestrol acetate Mirtazapine Nabilone Nandrolone Olanzapine Omega - 3 fatty acid Oxandrolone Pentoxifylline Prednisone Sugars Testosterone Thalidomide Endogenous ACTH / Corticotropin Adiponectin Agouti - related peptide Anandamide Cortisol / Hydrocortisone Cortisone Ghrelin Melanin - concentrating hormone Melatonin Neuropeptide Y Orexin / Hypocretin Melanocortin receptor modulators MC Agonists : ACTH ( corticotropin ) Afamelanotide ( melanotan I ) BMS - 470539 Bremelanotide HS - 014 HS - 024 MSH ( α, β, γ ) Melanotan II Modimelanotide PL - 8177 SHU - 8914 SHU - 9005 SHU - 9119 SNAP - 7941 Antagonists : ASIP MC Agonists : ACTH ( corticotropin ) Alsactide Codactide Giractide Norleusactide ( pentacosactride ) Seractide Tetracosactide ( tetracosactrin, cosyntropin ) Tosactide ( octacosactrin ) Tricosactide Tridecactide MC Agonists : ACTH ( corticotropin ) Afamelanotide ( melanotan I ) Bremelanotide MSH ( α, β, γ ) Melanotan II Modimelanotide PG - 931 Antagonists : AGRP ASIP HS - 014 ML - 00253764 PG - 106 SHU - 8914 SHU - 9005 SHU - 9119 MC Agonists : ACTH ( corticotropin ) Afamelanotide ( melanotan I ) AZD2820 BIM - 22493 Bremelanotide LY - 2112688 MSH ( α, β, γ ) Melanotan II MK - 0493 Modimelanotide PF - 00446687 PG - 931 PL - 6983 Ro 27 - 3225 Setmelanotide THIQ Antagonists : AGRP ASIP HS - 014 HS - 024 HS - 131 JKC - 363 MCL - 0020 MCL - 0042 MCL - 0129 ML - 00253764 MPB - 10 SHU - 8914 SHU - 9005 SHU - 9119 Unknown : Semax MC Agonists : ACTH ( corticotropin ) Afamelanotide ( melanotan I ) Bremelanotide HS - 014 HS - 024 MSH ( α, β, γ ) Melanotan II Modimelanotide SHU - 8914 SHU - 9005 SHU - 9119 Antagonists : ASIP ML - 00253764 Unknown : Semax Unsorted Agonists : Alsactide Codactide Giractide Norleusactide ( pentacosactride ) Seractide Tetracosactide ( tetracosactrin, cosyntropin ) Tosactide ( octacosactrin ) Tricosactide Tridecactide Others Propeptides : Lipotropin ( β, γ ) N - POMC ( NPP, pro-γ - MSH ) Proopiomelanocortin ( POMC ) See also : Receptor / signaling modulators Signaling peptide / protein receptor modulators Retrieved from `` https://en.wikipedia.org/w/index.php?title=Adrenocorticotropic_hormone&oldid=831994561 '' Categories : Genes on human chromosome 2 Anterior pituitary hormones Peptide hormones Melanocortin receptor agonists World Anti-Doping Agency prohibited substances Hidden categories : Articles with inconsistent citation formats CS1 maint : Uses authors parameter Use mdy dates from August 2017 Protein pages needing a picture All articles with unsourced statements Articles with unsourced statements from August 2015 Talk Contents About Wikipedia Български Català Čeština Dansk Deutsch ދިވެހިބަސް Ελληνικά Español Euskara فارسی Français Gaeilge Galego 한국어 Հայերեն Hrvatski Bahasa Indonesia Italiano עברית Қазақша Кыргызча Latina Lietuvių Magyar Македонски മലയാളം Nederlands 日本 語 Norsk Norsk nynorsk Oʻzbekcha / ўзбекча Polski Português Română Русский Shqip Slovenčina Српски / srpski Srpskohrvatski / српскохрватски Suomi Svenska தமிழ் Türkçe Українська 粵語 中文 38 more Edit links This page was last edited on 23 March 2018, at 05 : 21. 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Question: the hypothalamic hormone that triggers the release of adrenocorticotropic hormone
Answer: corticotropin-releasing hormone