Kortikotropin-oslobađajući hormon (CRH, originalno nazvan kortikotropin-oslobađajući faktor, CRF, takođe poznat kao kortikoliberin), je polipeptidnihormon i neurotransmiter koji učestvuje u odgovoru organizma na stres. On pripada familiji kortikotropin-oslobađajućih faktora.
Kortikotropin-oslobađajuči hormon je 41-aminokiselina dug peptid izveden iz 191-aminokiselinskog preprohormona. CRH izlučuje paraventrikularni nukleus (PVN) hipotalamusa u odgovoru na stres. Primetno umanjenje CRH koncentracije je bilo primećeno kod obolelih od Alchajmerove bolesti. Osim što se proizvodi u hipotalamusu, CRH je takođe sintetisan u perifernim tkivima, poput T limfocita, i visoko je izražen u posteljici. U posteljici je CRH služi kao indikator koji određuje dužinu gestacije i vreme porođaja. Brzo povišenje CRH nivoa u cirkulaciji se javlja na početku porođaja.[1]
Struktura
CRH su otkrili Vale et al. kod ovaca 1981.[2] Njegova sekvenca je:
SQEPPISLDLTFHLLREVLEMTKADQLAQQAHSNRKLLDIA
Peptidi pacova i čoveka su identični i razlikuju se od ovčije sekvence za samo 7 aminokiselina.[3]
↑Grammatopoulos, D K; Dai Y, Randeva H S, Levine M A, Karteris E, Easton A J, Hillhouse E W (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. (UNITED STATES) 13 (12): 2189–202. DOI:10.1210/me.13.12.2189. ISSN0888-8809. PMID10598591.
Florio P, Severi FM, Ciarmela P, et al. (2003). „Placental stress factors and maternal-fetal adaptive response: the corticotropin-releasing factor family”. Endocrine19 (1): 91–102. DOI:10.1385/ENDO:19:1:91. PMID12583606.
Florio P, Rossi M, Sigurdardottir M, et al. (2003). „Paracrine regulation of endometrial function: interaction between progesterone and corticotropin-releasing factor (CRF) and activin A”. Steroids68 (10–13): 801–7. DOI:10.1016/S0039-128X(03)00137-5. PMID14667971.
Vamvakopoulos NC, Karl M, Mayol V, et al. (1990). „Structural analysis of the regulatory region of the human corticotropin releasing hormone gene”. FEBS Lett.267 (1): 1–5. DOI:10.1016/0014-5793(90)80272-K. PMID2365075.
Arbiser JL, Morton CC, Bruns GA, Majzoub JA (1988). „Human corticotropin releasing hormone gene is located on the long arm of chromosome 8”. Cytogenet. Cell Genet.47 (3): 113–6. DOI:10.1159/000132525. PMID3259914.
Sasaki A, Tempst P, Liotta AS, et al. (1988). „Isolation and characterization of a corticotropin-releasing hormone-like peptide from human placenta”. J. Clin. Endocrinol. Metab.67 (4): 768–73. DOI:10.1210/jcem-67-4-768. PMID3262120.
Behan DP, Heinrichs SC, Troncoso JC, et al. (1995). „Displacement of corticotropin releasing factor from its binding protein as a possible treatment for Alzheimer's disease”. Nature378 (6554): 284–7. DOI:10.1038/378284a0. PMID7477348.
McLean M, Bisits A, Davies J, et al. (1995). „A placental clock controlling the length of human pregnancy”. Nat. Med.1 (5): 460–3. DOI:10.1038/nm0595-460. PMID7585095.
Slominski A, Ermak G, Hwang J, et al. (1995). „Proopiomelanocortin, corticotropin releasing hormone and corticotropin releasing hormone receptor genes are expressed in human skin”. FEBS Lett.374 (1): 113–6. DOI:10.1016/0014-5793(95)01090-2. PMID7589495.
Sutton SW, Behan DP, Lahrichi SL, et al. (1995). „Ligand requirements of the human corticotropin-releasing factor-binding protein”. Endocrinology136 (3): 1097–102. DOI:10.1210/en.136.3.1097. PMID7867564.
Vamvakopoulos NC, Chrousos GP (1994). „Structural organization of the 5' flanking region of the human corticotropin releasing hormone gene”. DNA Seq.4 (3): 197–206. DOI:10.3109/10425179309015632. PMID8161822.
Perrin MH, Donaldson CJ, Chen R, et al. (1994). „Cloning and functional expression of a rat brain corticotropin releasing factor (CRF) receptor”. Endocrinology133 (6): 3058–61. DOI:10.1210/en.133.6.3058. PMID8243338.
Romier C, Bernassau JM, Cambillau C, Darbon H (1993). „Solution structure of human corticotropin releasing factor by 1H NMR and distance geometry with restrained molecular dynamics”. Protein Eng.6 (2): 149–56. DOI:10.1093/protein/6.2.149. PMID8386360.
Liaw CW, Grigoriadis DE, Lovenberg TW, et al. (1997). „Localization of ligand-binding domains of human corticotropin-releasing factor receptor: a chimeric receptor approach”. Mol. Endocrinol.11 (7): 980–5. DOI:10.1210/me.11.7.980. PMID9178757.
Timpl P, Spanagel R, Sillaber I, et al. (1998). „Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1”. Nat. Genet.19 (2): 162–6. DOI:10.1038/520. PMID9620773.
Perone MJ, Murray CA, Brown OA, et al. (1998). „Procorticotrophin-releasing hormone: endoproteolytic processing and differential release of its derived peptides within AtT20 cells”. Mol. Cell. Endocrinol.142 (1–2): 191–202. DOI:10.1016/S0303-7207(98)00104-X. PMID9783915.
Willenberg HS, Bornstein SR, Hiroi N, et al. (2000). „Effects of a novel corticotropin-releasing-hormone receptor type I antagonist on human adrenal function”. Mol. Psychiatry5 (2): 137–41. DOI:10.1038/sj.mp.4000720. PMID10822340.
Saeed B, Fawcett M, Self C (2001). „Corticotropin-releasing hormone binding to the syncytiotrophoblast membranes”. Eur. J. Clin. Invest.31 (2): 125–30. DOI:10.1046/j.1365-2362.2001.00770.x. PMID11168450.
1go9: Praćenje strukturnih posledica PHE12-->D-PHE12 i LEU15-->AIB15 supstitucije u kortikotropin-oslobađajućem hormonu: implikacije za dizajn CRH antagonista.
1goe: Praćenje strukturnih posledica PHE12-->D-PHE12 i LEU15-->AIB15 supstitucije u kortikotropin-oslobađajućem hormonu: implikacije za dizajn CRH antagonista.