11β-Hydroxysteroid dehydrogenase type 1

Mammalian protein found in humans vanc October 2020 11β-Hydroxysteroid dehydrogenase type 1, also known as cortisone reductase, is an NADPH-dependent enzyme highly expressed in key metabolic tissues including liver, adipose tissue, and the central nervous system. In these tissues, HSD11B1 reduces cortisone to the active hormone cortisol that activates glucocorticoid receptors. It belongs to the family of short-chain dehydrogenases. It is encoded by the HSD11B1 gene. Function The protein encoded by this gene is a microsomal enzyme that catalyzes the conversion of the stress hormone cortisol to the inactive metabolite cortisone. In addition, the encoded protein can catalyze the reverse reaction, the conversion of cortisone to cortisol. Too much cortisol can lead to central obesity, and a particular variation in this gene has been associated with obesity and insulin resistance in children. Two transcript variants encoding the same protein have been found for this gene. Entrez Gene: HSD11B1 hydroxysteroid (11-beta) dehydrogenase 1 https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=3290 500px|Cortisol-cortisone equilibrium|center Clinical significance 11β-HSD1 is inhibited by carbenoxolone, a drug typically used in the treatment of peptic ulcers. Moreover, 18alpha-glycyrrhizic acid from liquorice root was discovered as an inhibitor. Classen-Houben D, Schuster D, Da Cunha T, Odermatt A, Wolber G, Jordis U, Kueenburg B Selective inhibition of 11beta-hydroxysteroid dehydrogenase 1 by 18alpha-glycyrrhetinic acid but not 18beta-glycyrrhetinic acid The Journal of Steroid Biochemistry and Molecular Biology 113 3–5 248–52 February 2009 19429429 10.1016/j.jsbmb.2009.01.009 21938309 Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and hence may explain why aspirin improves glycemic control in type 2 diabetes. Nixon M, Wake DJ, Livingstone DE, Stimson RH, Esteves CL, Seckl JR, Chapman KE, Andrew R, Walker BR Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and in humans, mediating insulin sensitization Diabetes 61 4 790–6 April 2012 22357964 3314355 10.2337/db11-0931 Epigallocatechin gallate from green tea can also potently inhibit this enzyme; Hintzpeter J, Stapelfeld C, Loerz C, Martin HJ, Maser E Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1 PLOS ONE 9 1 e84468 3 January 2014 24404164 3880318 10.1371/journal.pone.0084468 2014PLoSO...984468H free green tea is a complex mixture of various phenolics with contents varying with production and processing, and some of the phenolics are known HDAC inhibitors that alter genetic expression. EGCG as usually consumed in green tea is poorly absorbed into the bloodstream. More research is needed to reach firm conclusions.None of this is supported here. December 2019 Emestedastat is a compound being developed as a potential treatment of Alzheimer's disease and depression that acts by inhibiting 11β-HSD1. See also Cortisone reductase deficiency 11β-hydroxysteroid dehydrogenase type 2 References Further reading 33em White PC, Mune T, Agarwal AK 11 beta-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess Endocrine Reviews 18 1 135–56 February 1997 10.1210/edrv.18.1.0288 9034789 free Agarwal AK Cortisol metabolism and visceral obesity: role of 11beta-hydroxysteroid dehydrogenase type I enzyme and reduced co-factor NADPH Endocrine Research 29 4 411–8 November 2003 14682470 10.1081/ERC-120026947 32163545 Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS, Hewison M, Stewart PM 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response Endocrine Reviews 25 5 831–66 October 2004 15466942 10.1210/er.2003-0031 free Wake DJ, Walker BR Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 in obesity Endocrine 29 1 101–8 February 2006 16622297 10.1385/ENDO:29:1:101 8906021 Tannin GM, Agarwal AK, Monder C, New MI, White PC The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization The Journal of Biological Chemistry 266 25 16653–8 September 1991 10.1016/S0021-9258(18)55351-5 1885595 free Graham DL, Oram JF Identification and characterization of a high density lipoprotein-binding protein in cell membranes by ligand blotting The Journal of Biological Chemistry 262 16 7439–42 June 1987 10.1016/S0021-9258(18)47584-9 3034894 free Whorwood CB, Mason JI, Ricketts ML, Howie AJ, Stewart PM Detection of human 11 beta-hydroxysteroid dehydrogenase isoforms using reverse-transcriptase-polymerase chain reaction and localization of the type 2 isoform to renal collecting ducts Molecular and Cellular Endocrinology 110 1–2 R7–12 April 1995 7545619 10.1016/0303-7207(95)03546-J 25070635 Mune T, Rogerson FM, Nikkilä H, Agarwal AK, White PC Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase Nature Genetics 10 4 394–9 August 1995 7670488 10.1038/ng0895-394 30848352 Ricketts ML, Verhaeg JM, Bujalska I, Howie AJ, Rainey WE, Stewart PM Immunohistochemical localization of type 1 11beta-hydroxysteroid dehydrogenase in human tissues The Journal of Clinical Endocrinology and Metabolism 83 4 1325–35 April 1998 10.1210/jcem.83.4.4706 9543163 10988572 free Calvo D, Gómez-Coronado D, Suárez Y, Lasunción MA, Vega MA Human CD36 is a high affinity receptor for the native lipoproteins HDL, LDL, and VLDL Journal of Lipid Research 39 4 777–88 April 1998 10.1016/S0022-2275(20)32566-9 9555943 free Odermatt A, Arnold P, Stauffer A, Frey BM, Frey FJ The N-terminal anchor sequences of 11beta-hydroxysteroid dehydrogenases determine their orientation in the endoplasmic reticulum membrane The Journal of Biological Chemistry 274 40 28762–70 October 1999 10497248 10.1074/jbc.274.40.28762 free Sriskanda V, Schwer B, Ho CK, Shuman S Mutational analysis of Escherichia coli DNA ligase identifies amino acids required for nick-ligation in vitro and for in vivo complementation of the growth of yeast cells deleted for CDC9 and LIG4 Nucleic Acids Research 27 20 3953–63 October 1999 10497258 148661 10.1093/nar/27.20.3953 Schutte BC, Bjork BC, Coppage KB, Malik MI, Gregory SG, Scott DJ, Brentzell LM, Watanabe Y, Dixon MJ, Murray JC A preliminary gene map for the Van der Woude syndrome critical region derived from 900 kb of genomic sequence at 1q32-q41 Genome Research 10 1 81–94 Jan 2000 10645953 310500 10.1101/gr.10.1.81 11 July 2025 Cooper MS, Walker EA, Bland R, Fraser WD, Hewison M, Stewart PM Expression and functional consequences of 11beta-hydroxysteroid dehydrogenase activity in human bone Bone 27 3 375–81 September 2000 10962348 10.1016/S8756-3282(00)00344-6 Reddy ST, Wadleigh DJ, Grijalva V, Ng C, Hama S, Gangopadhyay A, Shih DM, Lusis AJ, Navab M, Fogelman AM Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids Arteriosclerosis, Thrombosis, and Vascular Biology 21 4 542–7 April 2001 11304470 10.1161/01.ATV.21.4.542 free Pácha J, Lisá V, Miksík I Effect of cellular differentiation on 11beta-hydroxysteroid dehydrogenase activity in the intestine Steroids 67 2 119–26 February 2002 11755176 10.1016/S0039-128X(01)00143-X 568790 Albertin G, Tortorella C, Malendowicz LK, Aragona F, Neri G, Nussdorfer GG Human adrenal cortex and aldosterone secreting adenomas express both 11beta-hydroxysteroid dehydrogenase type 1 and type 2 genes International Journal of Molecular Medicine 9 5 495–8 May 2002 11956655 10.3892/ijmm.9.5.495 Mazzocchi G, Malendowicz LK, Aragona F, Tortorella C, Gottardo L, Nussdorfer GG 11beta-Hydroxysteroid dehydrogenase types 1 and 2 are up- and downregulated in cortisol-secreting adrenal adenomas Journal of Investigative Medicine 50 4 288–92 July 2002 12109593 https://jim.bmj.com/lookup/pmidlookup?view=long&pmid=12109593 3290 External links HSD11B1 Biology no Category:EC 1.1.1 Category:Human proteins *