Corticosteroid 11-β-dehydrogenase isozyme 2 also known as 11-β-hydroxysteroid dehydrogenase 2 is an enzyme that in humans is encoded by the HSD11B2gene.[5][6][7]
Corticosteroid 11-β-dehydrogenase isozyme 2 is an NAD+-dependent enzyme expressed in aldosterone-selective epithelial tissues such as the kidney, colon, salivary and sweat glands. HSD211B2 expression is also found in the brainstem in a small, aldosterone-sensitive subset of neurons located in the nucleus of the solitary tract referred to as HSD2 neurons.[8]
In these tissues, HSD11B2 oxidizes the glucocorticoid cortisol to the inactive metabolite cortisone, thus preventing illicit activation of the mineralocorticoid receptor. This protective mechanism is necessary because cortisol circulates at 100- to 1000-fold higher concentrations than aldosterone, and binds with equal affinity to the mineralocorticoid receptor, thereby out-competing aldosterone in cells that do not produce HSD11B2.
This glucocorticoid-inactivating enzyme is also expressed in tissues that do not express the mineralocorticoid receptor, such as the placenta and testis, as well as parts of the developing brain, including the rhombencephalic progenitor cells that proliferate into cerebellar granule cells. In these tissues, HSD11B2 protects cells from the growth-inhibiting and/or pro-apoptotic effects of cortisol, particularly during embryonic development.
^ abcGRCh38: Ensembl release 89: ENSG00000176387 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000031891 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Albiston AL, Obeyesekere VR, Smith RE, Krozowski ZS (November 1994). "Cloning and tissue distribution of the human 11 beta-hydroxysteroid dehydrogenase type 2 enzyme". Mol. Cell. Endocrinol. 105 (2): R11–7. doi:10.1016/0303-7207(94)90176-7. PMID 7859916. S2CID 8240801.
^Brown RW, Chapman KE, Kotelevtsev Y, Yau JL, Lindsay RS, Brett L, Leckie C, Murad P, Lyons V, Mullins JJ, Edwards CR, Seckl JR (February 1996). "Cloning and production of antisera to human placental 11 beta-hydroxysteroid dehydrogenase type 2". Biochem. J. 313 (Pt 3): 1007–17. doi:10.1042/bj3131007. PMC1216963. PMID 8611140.
^Geerling, Joel C.; Arthur D. Loewy (September 2009). "Aldosterone in the brain". American Journal of Physiology. Renal Physiology. 297 (3): F559–76. doi:10.1152/ajprenal.90399.2008. PMC2739715. PMID 19261742.
Further readingedit
White PC, Mune T, Agarwal AK (1997). "11 beta-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess". Endocr. Rev. 18 (1): 135–56. doi:10.1210/edrv.18.1.0288. PMID 9034789.
Wilson RC, Dave-Sharma S, Wei JQ, et al. (1998). "A genetic defect resulting in mild low-renin hypertension". Proc. Natl. Acad. Sci. U.S.A. 95 (17): 10200–5. Bibcode:1998PNAS...9510200W. doi:10.1073/pnas.95.17.10200. PMC21485. PMID 9707624.
Quinkler M, Stewart PM (2003). "Hypertension and the cortisol-cortisone shuttle". J. Clin. Endocrinol. Metab. 88 (6): 2384–92. doi:10.1210/jc.2003-030138. PMID 12788832.
Tomlinson JW, Walker EA, Bujalska IJ, et al. (2005). "11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response". Endocr. Rev. 25 (5): 831–66. doi:10.1210/er.2003-0031. PMID 15466942.
Persu A (2005). "11beta-Hydroxysteroid deshydrogenase: a multi-faceted enzyme". J. Hypertens. 23 (1): 29–31. doi:10.1097/00004872-200501000-00007. PMID 15643119.
Funder JW, Pearce PT, Smith R, Smith AI (1988). "Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated". Science. 242 (4878): 583–5. Bibcode:1988Sci...242..583F. doi:10.1126/science.2845584. PMID 2845584.
Stewart PM, Wallace AM, Valentino R, et al. (1987). "Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age". Lancet. 2 (8563): 821–4. doi:10.1016/S0140-6736(87)91014-2. PMID 2889032. S2CID 42872913.
Wilson RC, Harbison MD, Krozowski ZS, et al. (1995). "Several homozygous mutations in the gene for 11 beta-hydroxysteroid dehydrogenase type 2 in patients with apparent mineralocorticoid excess". J. Clin. Endocrinol. Metab. 80 (11): 3145–50. doi:10.1210/jcem.80.11.7593417. PMID 7593417.
Wilson RC, Krozowski ZS, Li K, et al. (1995). "A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess". J. Clin. Endocrinol. Metab. 80 (7): 2263–6. doi:10.1210/jcem.80.7.7608290. PMID 7608290.
Krozowski Z, Baker E, Obeyesekere V, Callen DF (1995). "Localization of the gene for human 11 beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) to chromosome band 16q22". Cytogenet. Cell Genet. 71 (2): 124–5. doi:10.1159/000134089. PMID 7656579.
Mune T, Rogerson FM, Nikkilä H, et al. (1995). "Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase". Nat. Genet. 10 (4): 394–9. doi:10.1038/ng0895-394. PMID 7670488. S2CID 30848352.
Agarwal AK, Rogerson FM, Mune T, White PC (1996). "Gene structure and chromosomal localization of the human HSD11K gene encoding the kidney (type 2) isozyme of 11 beta-hydroxysteroid dehydrogenase". Genomics. 29 (1): 195–9. doi:10.1006/geno.1995.1231. PMID 8530071.
Krozowski Z, Albiston AL, Obeyesekere VR, et al. (1996). "The human 11 beta-hydroxysteroid dehydrogenase type II enzyme: comparisons with other species and localization to the distal nephron". J. Steroid Biochem. Mol. Biol. 55 (5–6): 457–64. doi:10.1016/0960-0760(95)00194-8. PMID 8547170. S2CID 12550923.
Brown RW, Chapman KE, Murad P, et al. (1996). "Purification of 11 beta-hydroxysteroid dehydrogenase type 2 from human placenta utilizing a novel affinity labelling technique". Biochem. J. 313 (Pt 3): 997–1005. doi:10.1042/bj3130997. PMC1217009. PMID 8611186.
Kitanaka S, Katsumata N, Tanae A, et al. (1998). "A new compound heterozygous mutation in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess". J. Clin. Endocrinol. Metab. 82 (12): 4054–8. doi:10.1210/jcem.82.12.4455. PMID 9398712.
Dave-Sharma S, Wilson RC, Harbison MD, et al. (1998). "Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess". J. Clin. Endocrinol. Metab. 83 (7): 2244–54. doi:10.1210/jcem.83.7.4986. PMID 9661590.
Li A, Tedde R, Krozowski ZS, et al. (1998). "Molecular basis for hypertension in the "type II variant" of apparent mineralocorticoid excess". Am. J. Hum. Genet. 63 (2): 370–9. doi:10.1086/301955. PMC1377297. PMID 9683587.
corticosteroid, beta, dehydrogenase, isozyme, corticosteroid, dehydrogenase, isozyme, also, known, hydroxysteroid, dehydrogenase, enzyme, that, humans, encoded, hsd11b2, gene, hsd11b2identifiersaliaseshsd11b2, ame1, hsd11k, hsd2, sdr9c3, hydroxysteroid, beta, . Corticosteroid 11 b dehydrogenase isozyme 2 also known as 11 b hydroxysteroid dehydrogenase 2 is an enzyme that in humans is encoded by the HSD11B2 gene 5 6 7 HSD11B2IdentifiersAliasesHSD11B2 AME AME1 HSD11K HSD2 SDR9C3 hydroxysteroid 11 beta dehydrogenase 2 hydroxysteroid 11 beta dehydrogenase 2External IDsOMIM 614232 MGI 104720 HomoloGene 20088 GeneCards HSD11B2 OMA HSD11B2 orthologsGene location Human Chr Chromosome 16 human 1 Band16q22 1Start67 430 652 bp 1 End67 437 553 bp 1 Gene location Mouse Chr Chromosome 8 mouse 2 Band8 D3 8 53 04 cMStart106 245 387 bp 2 End106 250 620 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inrenal medullarectumkidneyparotid glandskin of abdomenminor salivary glandskidney tubuleplacentaglomerulusmetanephric glomerulusTop expressed inleft colonuterusyolk sackidneycervixsacculeabdominal wallmedullary collecting ductotic placodecumulus cellMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionNAD binding steroid binding oxidoreductase activity 11 beta hydroxysteroid dehydrogenase NAD P activity Cellular componentcytoplasm endoplasmic reticulum membrane intracellular membrane bounded organelle endoplasmic reticulumBiological processresponse to hypoxia glucocorticoid metabolic process female pregnancy response to steroid hormone response to glucocorticoid response to insulin glucocorticoid biosynthetic process regulation of blood volume by renal aldosterone response to foodSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez329115484EnsemblENSG00000176387ENSMUSG00000031891UniProtP80365P51661RefSeq mRNA NM 000196NM 008289RefSeq protein NP 000187NP 032315Location UCSC Chr 16 67 43 67 44 MbChr 8 106 25 106 25 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Clinical significance 3 References 4 Further readingFunction editCorticosteroid 11 b dehydrogenase isozyme 2 is an NAD dependent enzyme expressed in aldosterone selective epithelial tissues such as the kidney colon salivary and sweat glands HSD211B2 expression is also found in the brainstem in a small aldosterone sensitive subset of neurons located in the nucleus of the solitary tract referred to as HSD2 neurons 8 In these tissues HSD11B2 oxidizes the glucocorticoid cortisol to the inactive metabolite cortisone thus preventing illicit activation of the mineralocorticoid receptor This protective mechanism is necessary because cortisol circulates at 100 to 1000 fold higher concentrations than aldosterone and binds with equal affinity to the mineralocorticoid receptor thereby out competing aldosterone in cells that do not produce HSD11B2 This glucocorticoid inactivating enzyme is also expressed in tissues that do not express the mineralocorticoid receptor such as the placenta and testis as well as parts of the developing brain including the rhombencephalic progenitor cells that proliferate into cerebellar granule cells In these tissues HSD11B2 protects cells from the growth inhibiting and or pro apoptotic effects of cortisol particularly during embryonic development Clinical significance editInhibition of this enzyme for example by the compound glycyrrhetinic acid enzymatically converted from glycyrrhizic acid found in natural liquorice results in a condition known as pseudohyperaldosteronism A genetically inherited deficiency of HSD11B2 is the underlying cause of the syndrome of apparent mineralocorticoid excess References edit a b c GRCh38 Ensembl release 89 ENSG00000176387 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000031891 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Albiston AL Obeyesekere VR Smith RE Krozowski ZS November 1994 Cloning and tissue distribution of the human 11 beta hydroxysteroid dehydrogenase type 2 enzyme Mol Cell Endocrinol 105 2 R11 7 doi 10 1016 0303 7207 94 90176 7 PMID 7859916 S2CID 8240801 Brown RW Chapman KE Kotelevtsev Y Yau JL Lindsay RS Brett L Leckie C Murad P Lyons V Mullins JJ Edwards CR Seckl JR February 1996 Cloning and production of antisera to human placental 11 beta hydroxysteroid dehydrogenase type 2 Biochem J 313 Pt 3 1007 17 doi 10 1042 bj3131007 PMC 1216963 PMID 8611140 Entrez Gene HSD11B2 hydroxysteroid 11 beta dehydrogenase 2 Geerling Joel C Arthur D Loewy September 2009 Aldosterone in the brain American Journal of Physiology Renal Physiology 297 3 F559 76 doi 10 1152 ajprenal 90399 2008 PMC 2739715 PMID 19261742 Further reading editWhite PC Mune T Agarwal AK 1997 11 beta Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess Endocr Rev 18 1 135 56 doi 10 1210 edrv 18 1 0288 PMID 9034789 Wilson RC Dave Sharma S Wei JQ et al 1998 A genetic defect resulting in mild low renin hypertension Proc Natl Acad Sci U S A 95 17 10200 5 Bibcode 1998PNAS 9510200W doi 10 1073 pnas 95 17 10200 PMC 21485 PMID 9707624 Quinkler M Stewart PM 2003 Hypertension and the cortisol cortisone shuttle J Clin Endocrinol Metab 88 6 2384 92 doi 10 1210 jc 2003 030138 PMID 12788832 Tomlinson JW Walker EA Bujalska IJ et al 2005 11beta hydroxysteroid dehydrogenase type 1 a tissue specific regulator of glucocorticoid response Endocr Rev 25 5 831 66 doi 10 1210 er 2003 0031 PMID 15466942 Persu A 2005 11beta Hydroxysteroid deshydrogenase a multi faceted enzyme J Hypertens 23 1 29 31 doi 10 1097 00004872 200501000 00007 PMID 15643119 Funder JW Pearce PT Smith R Smith AI 1988 Mineralocorticoid action target tissue specificity is enzyme not receptor mediated Science 242 4878 583 5 Bibcode 1988Sci 242 583F doi 10 1126 science 2845584 PMID 2845584 Stewart PM Wallace AM Valentino R et al 1987 Mineralocorticoid activity of liquorice 11 beta hydroxysteroid dehydrogenase deficiency comes of age Lancet 2 8563 821 4 doi 10 1016 S0140 6736 87 91014 2 PMID 2889032 S2CID 42872913 Wilson RC Harbison MD Krozowski ZS et al 1995 Several homozygous mutations in the gene for 11 beta hydroxysteroid dehydrogenase type 2 in patients with apparent mineralocorticoid excess J Clin Endocrinol Metab 80 11 3145 50 doi 10 1210 jcem 80 11 7593417 PMID 7593417 Wilson RC Krozowski ZS Li K et al 1995 A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess J Clin Endocrinol Metab 80 7 2263 6 doi 10 1210 jcem 80 7 7608290 PMID 7608290 Krozowski Z Baker E Obeyesekere V Callen DF 1995 Localization of the gene for human 11 beta hydroxysteroid dehydrogenase type 2 HSD11B2 to chromosome band 16q22 Cytogenet Cell Genet 71 2 124 5 doi 10 1159 000134089 PMID 7656579 Mune T Rogerson FM Nikkila H et al 1995 Human hypertension caused by mutations in the kidney isozyme of 11 beta hydroxysteroid dehydrogenase Nat Genet 10 4 394 9 doi 10 1038 ng0895 394 PMID 7670488 S2CID 30848352 Agarwal AK Rogerson FM Mune T White PC 1996 Gene structure and chromosomal localization of the human HSD11K gene encoding the kidney type 2 isozyme of 11 beta hydroxysteroid dehydrogenase Genomics 29 1 195 9 doi 10 1006 geno 1995 1231 PMID 8530071 Krozowski Z Albiston AL Obeyesekere VR et al 1996 The human 11 beta hydroxysteroid dehydrogenase type II enzyme comparisons with other species and localization to the distal nephron J Steroid Biochem Mol Biol 55 5 6 457 64 doi 10 1016 0960 0760 95 00194 8 PMID 8547170 S2CID 12550923 Brown RW Chapman KE Murad P et al 1996 Purification of 11 beta hydroxysteroid dehydrogenase type 2 from human placenta utilizing a novel affinity labelling technique Biochem J 313 Pt 3 997 1005 doi 10 1042 bj3130997 PMC 1217009 PMID 8611186 Kitanaka S Katsumata N Tanae A et al 1998 A new compound heterozygous mutation in the 11 beta hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess J Clin Endocrinol Metab 82 12 4054 8 doi 10 1210 jcem 82 12 4455 PMID 9398712 Dave Sharma S Wilson RC Harbison MD et al 1998 Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess J Clin Endocrinol Metab 83 7 2244 54 doi 10 1210 jcem 83 7 4986 PMID 9661590 Li A Tedde R Krozowski ZS et al 1998 Molecular basis for hypertension in the type II variant of apparent mineralocorticoid excess Am J Hum Genet 63 2 370 9 doi 10 1086 301955 PMC 1377297 PMID 9683587 Portal nbsp Biology Retrieved from https en wikipedia org w index php title Corticosteroid 11 beta dehydrogenase isozyme 2 amp oldid 1176601381, wikipedia, wiki, book, books, library,
