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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/12/29 17:29:42」(JST)

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Adrenocorticotropic hormone (ACTH), also known as corticotropin, is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It 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 corticosteroids. A deficiency of ACTH is a cause of secondary adrenal insufficiency and an excess of it is a cause of Cushing’s syndrome.

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.^[1] 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 NPP, Melanotropin Gamma (γ-MSH), Potential Peptide, Corticotropin (Adrenocorticotropic Hormone, or ACTH), Melanotropin Alpha (Melanocyte-Stimulating Hormone, or α-MSH), Corticotropin-like Intermediate Peptide (CLIP), Lipotropin Beta (β-LPH), Lipotropin Gamma (γ-LPH), Melanotropin Beta (β-MSH), Beta-Endorphin, and Met-Enkephalin.

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.

ACTH is also related to the circadian rhythm in many organisms. The half-life of ACTH in human blood is about ten minutes.^{[citation needed]}

An excess of ACTH can cause Cushing's Syndrome.

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).^[2]

Function

ACTH stimulates secretion of glucocorticoid steroid hormones from adrenal cortex cells especially in the zona fasciculata of the adrenal. ACTH acts by binding to cell surface ACTH receptors, which are located primarily on adrenocortical cells of the adrenal cortex. ACTH receptor is a seven-membrane-spanning G protein-coupled receptor.^[3] Upon ligand binding, the receptor undergoes conformation changes that stimulate the enzyme adenylyl cyclase, which leads to an increase in intracellular cAMP^[4] 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 bio-availability 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.^[4] This effect is observed over several hours.^[4]

In addition to steroidogenic enzymes, ACTH also enhances transcription of mitochondrial genes that encode for subunits of mitochondrial oxidative phosphorylation systems.^[5] These actions are probably necessary to supply the enhanced energy needs of adrenocortical cells stimulated by ACTH.^[5]

Reference ranges for blood tests, showing adrenocorticotropic hormone (green at left) among the hormones with smallest concentration in the blood.

Synthetic ACTH

An active synthetic form of ACTH, consisting of the first 23 amino acids of native ACTH, was first synthesized by Klaus Hofmann at the University of Pittsburgh.^[6] ACTH is available as a synthetic derivative in the forms of cosyntropin, tradename Cortrosyn, and synacthen (synthetic ACTH). Both are very rarely used in place of glucocorticoids to treat secondary adrenal insufficiency in a hospital setting, but are used primarily to conduct the ACTH stimulation test.

ACTH was first synthesized as a replacement for Acthar Gel, a long-lasting animal product used to treat infantile spasms. Once relatively inexpensive, Acthar Gel is currently an extremely expensive pharmaceutical product. Prices per vial have been as high as $60,000.^[7]

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

References

^ "Adrenocorticotropic Hormone (ACTH)". http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/acth.html.
^ PROOPIOMELANOCORTIN; NCBI --> POMC Retrieved on September 28, 2009
^ Raikhinstein, M.; Zohar, M.; Hanukoglu, I. (Feb 1994). "cDNA cloning and sequence analysis of the bovine adrenocorticotropic hormone (ACTH) receptor.". Biochim Biophys Acta 1220 (3): 329–32. PMID 8305507.
^ ^a ^b ^c Hanukoglu I, Feuchtwanger R, Hanukoglu A (Nov 1990). "Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells.". J Biol Chem 265 (33): 20602–8. PMID 2173715. http://www.jbc.org/content/265/33/20602.full.pdf.
^ ^a ^b Raikhinstein, M.; Hanukoglu, I. (Nov 1993). "Mitochondrial-genome-encoded RNAs: differential regulation by corticotropin in bovine adrenocortical cells.". Proc Natl Acad Sci U S A 90 (22): 10509–13. PMID 7504267.
^ "Simulated ACTH". Time. December 12, 1960. http://www.time.com/time/magazine/article/0,9171,871916,00.html.
^ "H.P. Acthar Gel and Cosyntropin Review". May 2009. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697107/.

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The acute effect of ethanol on adrenal cortex in female rats--possible role of nitric oxide.

Dikic D, Budec M, Vranjes-Duric S, Koko V, Vignjevic S, Mitrovic O.SourceCorresponding author: dragoslava@imi.bg.ac.rs.
Alcohol and alcoholism (Oxford, Oxfordshire).Alcohol Alcohol.2011 Sep-Oct;46(5):523-8. Epub 2011 May 24.
AIMS: The present study was designed to investigate a possible role of endogenous nitric oxide (NO) in the adrenal response to an acute alcohol administration in female rats. To this end, N(ω)-nitro-l-arginine-methyl ester (l-NAME), a competitive inhibitor of all isoforms of NO synthase, was used.M
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Validation of a cortisol enzyme immunoassay and characterization of salivary cortisol circadian rhythm in chimpanzees (Pan troglodytes).

Heintz MR, Santymire RM, Parr LA, Lonsdorf EV.SourceCommittee on Evolutionary Biology, University of Chicago, Chicago, Illinois. mheintz@uchicago.edu.
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Monitoring concentrations of stress hormones is an important tool for behavioral research and conservation for animals both in the wild and captivity. Glucocorticoids can be measured in mammals as an indicator of stress by analyzing blood, feces, urine, hair, feathers, or saliva. The advantages of u
PMID 21538448

Japanese Journal

ラット急性ストレス負荷による大腸運動亢進に対する中枢オキシトシンの抑制作用(シンポジウム:脳腸相関と腸管炎症,2010年,第51回日本心身医学会総会ならびに学術講演会(仙台))

金子宏,松永昌宏,坪井宏仁,川西陽子
心身医学 51(4), 323-328, 2011-04-01
不安,恐怖などのネガティブ感情やストレスは大腸運動を亢進させる.この作用機序として,ストレスによる中枢corticotropin-releasing factor(CRF)の増加の関与が示されている.われわれは,ラットの水回避ストレスモデルを用いて,ストレス緩和作用をもつオキシトシンの,ストレス負荷時の大腸運動への効果を明らかにすることを試みた.その結果,脳室内へのオキシトシン投与は,ストレスによ …
NAID 110008593581

ラット急性ストレス負荷による大腸運動亢進に対する中枢オキシトシンの抑制作用 (第51回日本心身医学会総会ならびに学術講演会シンポジウム/脳腸相関と腸管炎症)

金子宏,松永昌宏,坪井宏仁 [他]
心身医学 51(4), 323-328, 2011
NAID 40018730811

Related Pictures

★リンクテーブル★

リンク元	「コルチコトロピン」「adrenocorticotrophic hormone」「corticotropin zinc hydroxide」

「コルチコトロピン」

proopiomelanocortin (adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/ beta-melanocyte stimulating hormone/ beta-endorphin)
Identifiers
Symbol	POMC
Entrez	5443
HUGO	9201
OMIM	176830
RefSeq	NM_000939
UniProt	P01189
Other data
Locus	Chr. 2 p23