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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/05/22 13:06:00」(JST)

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Corticotropin-releasing hormone (CRH) also known as corticotropin-releasing factor (CRF) or corticoliberin is a peptide hormone and neurotransmitter involved in the stress response. It is a releasing hormone that belongs to corticotropin-releasing factor family. In humans, it is encoded by the CRH gene.^[1]

Its main function is the stimulation of the pituitary synthesis of ACTH, as part of the HPA Axis.

Corticotropin-releasing hormone (CRH) is a 41-amino acid peptide derived from a 196-amino acid preprohormone. CRH is secreted by the paraventricular nucleus (PVN) of the hypothalamus in response to stress. Increased CRH production has been observed to be associated with Alzheimer's disease and major depression,^[2] and autosomal recessive hypothalamic corticotropin deficiency has multiple and potentially fatal metabolic consequences including hypoglycemia.^[1] In addition to being produced in the hypothalamus, CRH is also synthesized in peripheral tissues, such as T lymphocytes, and is highly expressed in the placenta. In the placenta, CRH is a marker that determines the length of gestation and the timing of parturition and delivery. A rapid increase in circulating levels of CRH occurs at the onset of parturition, suggesting that, in addition to its metabolic functions, CRH may act as a trigger for parturition.^[1]

A recombinant version for diagnostics is called corticorelin (INN).

Hormonal actions

CRH is produced by parvocellular neuroendocrine cells within the paraventricular nucleus of the hypothalamus and is released at the median eminence from neurosecretory terminals of these neurons into the primary capillary plexus of the hypothalamo-hypophyseal portal system. The portal system carries the CRH to the anterior lobe of the pituitary, where it stimulates corticotropes to secrete adrenocorticotropic hormone (ACTH) and other biologically-active substances (β-endorphin). ACTH stimulates the synthesis of cortisol, glucocorticoids, mineralocorticoids and DHEA.^[3]

In the short term, CRH can suppress appetite, increase subjective feelings of anxiety, and perform other functions like boosting attention. Although the distal action of CRH is immunosuppression via the action of cortisol, CRH itself can actually heighten inflammation, a process being investigated in multiple sclerosis research.^[4]

Psychopharmacology

The CRH-1 receptor antagonist pexacerfont is currently under investigation for the treatment of generalized anxiety disorder.^[5] Another CRH-1 antagonist antalarmin has been researched in animal studies for the treatment of anxiety, depression and other conditions, but no human trials with this compound have been carried out.

Also, abnormally high levels of CRH have been found in the cerebrospinal fluid of people that have committed suicide.^[6]

Recent research has linked the activation of the CRH1 receptor with the euphoric feelings that accompany alcohol consumption. A CRH1 receptor antagonist developed by Pfizer, CP-154,526 is under investigation for the potential treatment of alcoholism.^[7]^[8]

Alpha-helical CRH-(9–41) acts as a CRH antagonist.^[9]

Role in parturition

CRH is also synthesized by the placenta and seems to determine the duration of pregnancy.^[10]

Levels rise towards the end of pregnancy just before birth and current theory suggests three roles of CRH in parturition:^[11]

Increases levels of dehydroepiandrosterone (DHEA) directly by action on the fetal adrenal gland, and indirectly via the mother's pituitary gland. DHEA has a role in preparing for and stimulating cervical contractions.
Increases prostaglandin availability in uteroplacental tissues. Prostaglandins activate cervical contractions.
Prior to parturition it may have a role inhibiting contractions, through increasing cAMP levels in the myometrium.

In culture, trophoblast CRH is inhibited by progesterone, which remains high throughout pregnancy. Its release is stimulated by glucocorticoids and catecholamines, which increase prior to parturition lifting this progesterone block.^[12]

Structure

The 41-amino acid sequence of CRH was first discovered in sheep by Vale et al. in 1981.^[13] Its full sequence is:

SQEPPISLDLTFHLLREVLEMTKADQLAQQAHSNRKLLDIA

The rat and human peptides are identical and differ from the ovine sequence only by 7 amino acids.^[14]

SEEPPISLDLTFHLLREVLEMARAEQLAQQAHSNRKLMEII

Role in non-mammalian vertebrates

In mammals, studies suggest that CRH has no significant thyrotropic effect. However, in representatives of all non-mammalian vertebrates, it has been found that, in addition to its corticotropic function, CRH has a potent thyrotropic function, acting with TRH to control the thyroid axis (TRH has been found to be less potent than CRH in some species).^[15]^[16]

Interactions

Corticotropin-releasing hormone has been shown to interact with corticotropin-releasing hormone receptor 1.^[17]^[18]

References

^ ^a ^b ^c "Entrez Gene: CRH corticotropin releasing hormone".
^ Raadsheer FC, van Heerikhuize JJ, Lucassen PJ, Hoogendijk WJ, Tilders FJ, Swaab DF (September 1995). "Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression". Am J Psychiatry 152 (9): 1372–6. PMID 7653697.
^ "Corticotrophin-releasing hormone". September 5, 2012. Society for Endocrinology.
^ Paul, William E. (September 1993). "Infectious Diseases and the Immune System". Scientific American 269 (3): 112. Bibcode:1993SciAm.269c..90P. doi:10.1038/scientificamerican0993-90.
^ "Study of Pexacerfont (BMS-562086) in the Treatment of Outpatients With Generalized Anxiety Disorder". ClinicalTrials.gov. 2008-08-01. Retrieved 2008-08-03.
^ Arató M, Bánki CM, Bissette G, Nemeroff CB (1989). "Elevated CSF CRF in suicide victims". Biol. Psychiatry 25 (3): 355–9. doi:10.1016/0006-3223(89)90183-2. PMID 2536563.
^ "Drug Has Potential To Prevent Alcoholics From Relapsing". Science News. ScienceDaily. 2008-08-02. Retrieved 2008-08-09.
^ Pastor R, McKinnon CS, Scibelli AC, Burkhart-Kasch S, Reed C, Ryabinin AE, Coste SC, Stenzel-Poore MP, Phillips TJ (July 2008). "Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: a urocortin1-independent mechanism". Proc. Natl. Acad. Sci. U.S.A. 105 (26): 9070–5. Bibcode:2008PNAS..105.9070P. doi:10.1073/pnas.0710181105. PMC 2449366. PMID 18591672.
^ Santos J, Saunders PR, Hanssen NP, Yang PC, Yates D, Groot JA, Perdue MH (1 August 1999). "Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat". Am. J. Physiol. 277 (2 Pt 1): G391–9. PMID 10444454.
^ Kimball JW (2006-06-15). "Hormones of the Hypothalamus". Kimball's Biology Pages. Retrieved 2008-08-03.
^ Lye S, Challis JRG (2001). "Chapter 12: Parturition". In Bocking AD, Harding R. Fetal growth and development. Cambridge, UK: Cambridge University Press. pp. 241–266. ISBN 0-521-64543-3.
^ Jones SA, Brooks AN, Challis JR (April 1989). "Steroids modulate corticotropin-releasing hormone production in human fetal membranes and placenta". J. Clin. Endocrinol. Metab. 68 (4): 825–30. doi:10.1210/jcem-68-4-825. PMID 2537843.
^ Vale W, Spiess J, Rivier C, Rivier J (September 1981). "Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin". Science 213 (4514): 1394–7. Bibcode:1981Sci...213.1394V. doi:10.1126/science.6267699. PMID 6267699.
^ Chrousos GP, Schuermeyer TH, Doppman J, Oldfield EH, Schulte HM, Gold PW, Loriaux DL (March 1985). "NIH conference. Clinical applications of corticotropin-releasing factor". Annals of Internal Medicine 102 (3): 344–358. doi:10.7326/0003-4819-102-3-344. PMID 2982307.
^ Seasholtz AF, Valverde RA, Denver RJ (October 2002). "Corticotropin-releasing hormone-binding protein: biochemistry and function from fishes to mammals". The Journal of endocrinology 175 (1): 89–97. doi:10.1677/joe.0.1750089. PMID 12379493.
^ De Groef B, Van der Geyten S, Darras VM, Kühn ER (March 2006). "Role of corticotropin-releasing hormone as a thyrotropin-releasing factor in non-mammalian vertebrates". General and comparative endocrinology 146 (1): 62–8. doi:10.1016/j.ygcen.2005.10.014. PMID 16337947.
^ Grammatopoulos DK, Dai Y, Randeva HS, Levine MA, Karteris E, Easton AJ, Hillhouse EW (December 1999). "A novel spliced variant of the type 1 corticotropin-releasing hormone receptor with a deletion in the seventh transmembrane domain present in the human pregnant term myometrium and fetal membranes". Mol. Endocrinol. 13 (12): 2189–202. doi:10.1210/me.13.12.2189. PMID 10598591.
^ Gottowik J, Goetschy V, Henriot S, Kitas E, Fluhman B, Clerc RG, Moreau JL, Monsma FJ, Kilpatrick GJ (October 1997). "Labelling of CRF1 and CRF2 receptors using the novel radioligand, [3H]-urocortin". Neuropharmacology 36 (10): 1439–46. doi:10.1016/S0028-3908(97)00098-1. PMID 9423932.

English Journal

Related Pictures

Corticotropin releasing hormone Wallpaper Corticotropin-releasing hormone About 'Corticotropin releasing hormone' des Hypothalamus CRH – Corticoliberin Image of Corticotropin releasing hormone Corticotropin-releasing factor complex von Corticoliberin im Blut eines Makaken

★リンクテーブル★

リンク元	「コルチコリベリン」

「コルチコリベリン」

CRH
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3EHU, 3EHT, 1GOE
Identifiers
Aliases	CRH, CRF, 1
External IDs	OMIM: 122560 MGI: 88496 HomoloGene: 599 GeneCards: 1392
Gene ontology
Molecular function	• hormone activity; • corticotropin-releasing hormone receptor 1 binding; • corticotropin-releasing hormone receptor 2 binding; • protein binding; • neuropeptide hormone activity; • receptor binding;
Cellular component	• cytoplasm; • perikaryon; • varicosity; • extracellular space; • extracellular region; • neuronal cell body;
Biological process	• response to cocaine; • response to immobilization stress; • positive regulation of cAMP biosynthetic process; • positive regulation of cortisol secretion; • steroid metabolic process; • positive regulation of protein phosphorylation; • negative regulation of luteinizing hormone secretion; • positive regulation of cell death; • associative learning; • negative regulation of glucagon secretion; • negative regulation of epinephrine secretion; • ion homeostasis; • lung development; • negative regulation of blood pressure; • diterpenoid metabolic process; • response to corticosterone; • female pregnancy; • negative regulation of norepinephrine secretion; • adrenal gland development; • positive regulation of corticotropin secretion; • synaptic transmission, dopaminergic; • negative regulation of cell death; • negative regulation of gene expression; • cellular response to dexamethasone stimulus; • positive regulation of corticosterone secretion; • response to estrogen; • locomotory exploration behavior; • regulation of N-methyl-D-aspartate selective glutamate receptor activity; • regulation of serotonin secretion; • positive regulation of calcium ion import; • glucocorticoid biosynthetic process; • positive regulation of gene expression; • positive regulation of digestive system process; • parturition; • response to pain; • positive regulation of circadian sleep/wake cycle, wakefulness; • positive regulation of cell proliferation; • hypothalamus development; • learning or memory; • hormone-mediated apoptotic signaling pathway; • positive regulation of insulin secretion involved in cellular response to glucose stimulus; • response to ethanol; • inflammatory response; • negative regulation of circadian sleep/wake cycle, REM sleep; • response to ether; • positive regulation of behavioral fear response; • response to drug; • signal transduction; • cellular response to cocaine; • long-term synaptic potentiation; • synaptic transmission;
	Sources:Amigo / QuickGO
RNA expression pattern
	; ;
	More reference expression data
Orthologs
	1392
	12918
	ENSG00000147571
	ENSMUSG00000049796
	P06850
	Q8CIT0
	NM_000756
	NM_205769
	NP_000747.1
	NP_991338.1
	Wikidata
View/Edit Human	View/Edit Mouse

　　[★]

英: corticoliberin
関: 副腎皮質刺激ホルモン放出ホルモン

[entrez-1] "Entrez Gene: CRH corticotropin releasing hormone".

[pmid7653697-2] Raadsheer FC, van Heerikhuize JJ, Lucassen PJ, Hoogendijk WJ, Tilders FJ, Swaab DF (September 1995). "Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression". Am J Psychiatry 152 (9): 1372–6. PMID 7653697.

[3] "Corticotrophin-releasing hormone". September 5, 2012. Society for Endocrinology.

[4] Paul, William E. (September 1993). "Infectious Diseases and the Immune System". Scientific American 269 (3): 112. Bibcode:1993SciAm.269c..90P. doi:10.1038/scientificamerican0993-90.

[url_Study_ClinicalTrials.gov-5] "Study of Pexacerfont (BMS-562086) in the Treatment of Outpatients With Generalized Anxiety Disorder". ClinicalTrials.gov. 2008-08-01. Retrieved 2008-08-03.

[6] Arató M, Bánki CM, Bissette G, Nemeroff CB (1989). "Elevated CSF CRF in suicide victims". Biol. Psychiatry 25 (3): 355–9. doi:10.1016/0006-3223(89)90183-2. PMID 2536563.

[urlDrug_Has_Potential_To_Prevent_Alcoholics_From_Relapsing-7] "Drug Has Potential To Prevent Alcoholics From Relapsing". Science News. ScienceDaily. 2008-08-02. Retrieved 2008-08-09.

[pmid18591672-8] Pastor R, McKinnon CS, Scibelli AC, Burkhart-Kasch S, Reed C, Ryabinin AE, Coste SC, Stenzel-Poore MP, Phillips TJ (July 2008). "Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: a urocortin1-independent mechanism". Proc. Natl. Acad. Sci. U.S.A. 105 (26): 9070–5. Bibcode:2008PNAS..105.9070P. doi:10.1073/pnas.0710181105. PMC 2449366. PMID 18591672.

[pmid10444454-9] Santos J, Saunders PR, Hanssen NP, Yang PC, Yates D, Groot JA, Perdue MH (1 August 1999). "Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat". Am. J. Physiol. 277 (2 Pt 1): G391–9. PMID 10444454.

[urlHormones_of_the_Hypothalamus-10] Kimball JW (2006-06-15). "Hormones of the Hypothalamus". Kimball's Biology Pages. Retrieved 2008-08-03.

[isbn0-521-64543-3-11] Lye S, Challis JRG (2001). "Chapter 12: Parturition". In Bocking AD, Harding R. Fetal growth and development. Cambridge, UK: Cambridge University Press. pp. 241–266. ISBN 0-521-64543-3.

[pmid2537843-12] Jones SA, Brooks AN, Challis JR (April 1989). "Steroids modulate corticotropin-releasing hormone production in human fetal membranes and placenta". J. Clin. Endocrinol. Metab. 68 (4): 825–30. doi:10.1210/jcem-68-4-825. PMID 2537843.

[pmid6267699-13] Vale W, Spiess J, Rivier C, Rivier J (September 1981). "Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin". Science 213 (4514): 1394–7. Bibcode:1981Sci...213.1394V. doi:10.1126/science.6267699. PMID 6267699.

[pmid2982307-14] Chrousos GP, Schuermeyer TH, Doppman J, Oldfield EH, Schulte HM, Gold PW, Loriaux DL (March 1985). "NIH conference. Clinical applications of corticotropin-releasing factor". Annals of Internal Medicine 102 (3): 344–358. doi:10.7326/0003-4819-102-3-344. PMID 2982307.

[15] Seasholtz AF, Valverde RA, Denver RJ (October 2002). "Corticotropin-releasing hormone-binding protein: biochemistry and function from fishes to mammals". The Journal of endocrinology 175 (1): 89–97. doi:10.1677/joe.0.1750089. PMID 12379493.

[16] De Groef B, Van der Geyten S, Darras VM, Kühn ER (March 2006). "Role of corticotropin-releasing hormone as a thyrotropin-releasing factor in non-mammalian vertebrates". General and comparative endocrinology 146 (1): 62–8. doi:10.1016/j.ygcen.2005.10.014. PMID 16337947.

[pmid10598591-17] Grammatopoulos DK, Dai Y, Randeva HS, Levine MA, Karteris E, Easton AJ, Hillhouse EW (December 1999). "A novel spliced variant of the type 1 corticotropin-releasing hormone receptor with a deletion in the seventh transmembrane domain present in the human pregnant term myometrium and fetal membranes". Mol. Endocrinol. 13 (12): 2189–202. doi:10.1210/me.13.12.2189. PMID 10598591.

[pmid9423932-18] Gottowik J, Goetschy V, Henriot S, Kitas E, Fluhman B, Clerc RG, Moreau JL, Monsma FJ, Kilpatrick GJ (October 1997). "Labelling of CRF1 and CRF2 receptors using the novel radioligand, [3H]-urocortin". Neuropharmacology 36 (10): 1439–46. doi:10.1016/S0028-3908(97)00098-1. PMID 9423932.

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案内

corticoliberin