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 100-1000-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 progentitor 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.
^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. PMID7859916.
Funder JW, Pearce PT, Smith R, Smith AI (1988). "Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated". Science242 (4878): 583–5. doi:10.1126/science.2845584. PMID2845584.
Stewart PM, Wallace AM, Valentino R, et al. (1987). "Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age". Lancet2 (8563): 821–4. doi:10.1016/S0140-6736(87)91014-2. PMID2889032.
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/jc.80.11.3145. PMID7593417.
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/jc.80.7.2263. PMID7608290.
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. PMID7656579.
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. PMID7670488.
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". Genomics29 (1): 195–9. doi:10.1006/geno.1995.1231. PMID8530071.
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. PMID8547170.
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/jc.82.12.4054. PMID9398712.
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/jc.83.7.2244. PMID9661590.