Biology:Corticosteroid 11-beta-dehydrogenase isozyme 2

Short description: Enzyme found in humans

Generic protein structure example

Corticosteroid 11-β-dehydrogenase isozyme 2 also known as 11-β-hydroxysteroid dehydrogenase 2 is an enzyme that in humans is encoded by the HSD11B2 gene.

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.

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

• "11 beta-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess". Endocr. Rev. 18 (1): 135–56. 1997. 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. doi:10.1073/pnas.95.17.10200. PMID 9707624. Bibcode: 1998PNAS...9510200W. 
• "Hypertension and the cortisol-cortisone shuttle". J. Clin. Endocrinol. Metab. 88 (6): 2384–92. 2003. 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. 
• "Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated". Science 242 (4878): 583–5. 1988. doi:10.1126/science.2845584. PMID 2845584. Bibcode: 1988Sci...242..583F. 
• 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. 
• 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. 
• "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. 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. 
• "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. 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. 
• 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. 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. PMID 9683587.