Corticosteroid 11-beta-dehydrogenase isozyme 2 explained

Corticosteroid 11-β-dehydrogenase isozyme 2 also known as 11-β-hydroxysteroid dehydrogenase 2 is an enzyme that in humans is encoded by the gene.^{[1] [2] [3]}

Function

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.^[4]

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

Inhibition 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.

Further reading

• White PC, Mune T, Agarwal AK . 11 beta-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess . Endocr. Rev. . 18 . 1 . 135–56 . 1997 . 10.1210/edrv.18.1.0288 . 9034789 . free .
• Wilson RC . A genetic defect resulting in mild low-renin hypertension . Proc. Natl. Acad. Sci. U.S.A. . 95 . 17 . 10200–5 . 1998 . 9707624 . 10.1073/pnas.95.17.10200 . 21485 . vanc. Dave-Sharma S . Wei JQ . 3 . Obeyesekere . VR . Li . K . Ferrari . P . Krozowski . ZS . Shackleton . CH . Bradlow . L . 1998PNAS...9510200W . free .
• Quinkler M, Stewart PM . Hypertension and the cortisol-cortisone shuttle . J. Clin. Endocrinol. Metab. . 88 . 6 . 2384–92 . 2003 . 12788832 . 10.1210/jc.2003-030138 . free .
• Tomlinson JW . 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response . Endocr. Rev. . 25 . 5 . 831–66 . 2005 . 15466942 . 10.1210/er.2003-0031 . vanc. Walker EA . Bujalska IJ . 3 . Draper . N . Lavery . GG . Cooper . MS . Hewison . M . Stewart . PM . free .
• Persu A . 11beta-Hydroxysteroid deshydrogenase: a multi-faceted enzyme . J. Hypertens. . 23 . 1 . 29–31 . 2005 . 15643119 . 10.1097/00004872-200501000-00007. free .
• Funder JW, Pearce PT, Smith R, Smith AI . Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated . Science . 242 . 4878 . 583–5 . 1988 . 2845584 . 10.1126/science.2845584 . 1988Sci...242..583F .
• Stewart PM . Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age . Lancet . 2 . 8563 . 821–4 . 1987 . 2889032 . 10.1016/S0140-6736(87)91014-2 . vanc. Wallace AM . Valentino R . 3 . Burt . Daniel . Shackleton . Cedrich.L. . Edwards . Christopherr.W. . 42872913 .
• Wilson RC . 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 . 1995 . 7593417 . vanc. Harbison MD . Krozowski ZS . 3 . Funder . JW . Shackleton . CH . Hanauske-Abel . HM . Wei . JQ . Hertecant . J . Moran . A . 10.1210/jcem.80.11.7593417 .
• Wilson RC . A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess . J. Clin. Endocrinol. Metab. . 80 . 7 . 2263–6 . 1995 . 7608290 . vanc. Krozowski ZS . Li K . 3 . Obeyesekere . VR . Razzaghy-Azar . M . Harbison . MD . Wei . JQ . Shackleton . CH . Funder . JW . 10.1210/jcem.80.7.7608290 .
• Krozowski Z, Baker E, Obeyesekere V, Callen DF . Localization of the gene for human 11 beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) to chromosome band 16q22 . Cytogenet. Cell Genet. . 71 . 2 . 124–5 . 1995 . 7656579 . 10.1159/000134089 .
• Mune T . Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase . Nat. Genet. . 10 . 4 . 394–9 . 1995 . 7670488 . 10.1038/ng0895-394 . vanc. Rogerson FM . Nikkilä H . 3 . Agarwal . Anil K. . White . Perrin C. . 30848352 .
• Agarwal AK, Rogerson FM, Mune T, White PC . 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 . 1996 . 8530071 . 10.1006/geno.1995.1231 .
• Krozowski Z . 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 . 1996 . 8547170 . 10.1016/0960-0760(95)00194-8 . vanc. Albiston AL . Obeyesekere VR . 3 . Andrews . R.K. . Smith . R.E. . 12550923 .
• Brown RW . Purification of 11 beta-hydroxysteroid dehydrogenase type 2 from human placenta utilizing a novel affinity labelling technique . Biochem. J. . 313 . Pt 3. 997–1005 . 1996 . 8611186 . 10.1042/bj3130997. 1217009 . vanc. Chapman KE . Murad P . 3 . Edwards . CR . Seckl . JR .
• Kitanaka S . 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 . 1998 . 9398712 . vanc. Katsumata N . Tanae A . 3 . Hibi . I . Takeyama . K . Fuse . H . Kato . S . Tanaka . T . 10.1210/jcem.82.12.4455 . free .
• Dave-Sharma S . Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess . J. Clin. Endocrinol. Metab. . 83 . 7 . 2244–54 . 1998 . 9661590 . vanc. Wilson RC . Harbison MD . 3 . Newfield . R . Azar . MR . Krozowski . ZS . Funder . JW . Shackleton . CH . Bradlow . HL . 10.1210/jcem.83.7.4986 . free .
• Li A . Molecular basis for hypertension in the "type II variant" of apparent mineralocorticoid excess . Am. J. Hum. Genet. . 63 . 2 . 370–9 . 1998 . 9683587 . 10.1086/301955 . 1377297 . vanc. Tedde R . Krozowski ZS . 3 . Pala . A. . Li . K.X.Z. . Shackleton . C.H.L. . Mantero . F. . Palermo . M. . Stewart . P.M. .

Notes and References

1. Albiston AL, Obeyesekere VR, Smith RE, Krozowski ZS . Cloning and tissue distribution of the human 11 beta-hydroxysteroid dehydrogenase type 2 enzyme . Mol. Cell. Endocrinol. . 105 . 2 . R11–7 . November 1994 . 7859916 . 10.1016/0303-7207(94)90176-7. 8240801 .
2. Brown RW, Chapman KE, Kotelevtsev Y, Yau JL, Lindsay RS, Brett L, Leckie C, Murad P, Lyons V, Mullins JJ, Edwards CR, Seckl JR . Cloning and production of antisera to human placental 11 beta-hydroxysteroid dehydrogenase type 2 . Biochem. J. . 313 . Pt 3. 1007–17 . February 1996 . 8611140 . 1216963 . 10.1042/bj3131007.
3. Web site: Entrez Gene: HSD11B2 hydroxysteroid (11-beta) dehydrogenase 2.
4. Joel C. . Geerling . Arthur D. Loewy . September 2009 . Aldosterone in the brain . American Journal of Physiology. Renal Physiology . 297 . F559–76 . 19261742 . 3 . 10.1152/ajprenal.90399.2008 . 2739715 .