11-Beta-Hydroxysteroid Dehydrogenase Type 2 (HSD11b2)

AME; AME1; HSD11K; HSD2; SDR9C3; Short Chain Dehydrogenase/Reductase Family 9C,Member 3; NAD-dependent 11-beta-hydroxysteroid dehydrogenase

SPN	R619
HGNC	5209
MGI	104720
PubMed	12860834
RGD	2835
UniProt	P80365
Wiki	HSD11B2

Corticosteroid 11-beta-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.

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.

Reference

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Mol. Cell. Endocrinol. 105:R11-R17(1994) [PubMed] [Europe PMC] [Abstract]

"Gene structure and chromosomal localization of the human HSD11K gene encoding the kidney (type 2) isozyme of 11 beta-hydroxysteroid dehydrogenase."
Genomics 29:195-199(1995) [PubMed] [Europe PMC] [Abstract]

"Cloning and production of antisera to human placental 11 beta-hydroxysteroid dehydrogenase type 2."
Biochem. J. 313:1007-1017(1996) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Purification of 11 beta-hydroxysteroid dehydrogenase type 2 from human placenta utilizing a novel affinity labelling technique."
Biochem. J. 313:997-1005(1996) [PubMed] [Europe PMC] [Abstract]

"Several homozygous mutations in the gene for 11 beta-hydroxysteroid dehydrogenase type 2 in patients with apparent mineralocorticoid excess."
J. Clin. Endocrinol. Metab. 80:3145-3150(1995) [PubMed] [Europe PMC] [Abstract]

"Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age."
Lancet 2:821-824(1987) [PubMed] [Europe PMC] [Abstract]

"The intracellular localization of the mineralocorticoid receptor is regulated by 11beta-hydroxysteroid dehydrogenase type 2."
J. Biol. Chem. 276:28484-28492(2001) [PubMed] [Europe PMC] [Abstract]

"A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess."
J. Clin. Endocrinol. Metab. 80:2263-2266(1995) [PubMed] [Europe PMC] [Abstract]

"Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase."
Nat. Genet. 10:394-399(1995) [PubMed] [Europe PMC] [Abstract]

"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. 82:4054-4058(1997) [PubMed] [Europe PMC] [Abstract]

"Molecular basis for hypertension in the 'type II variant' of apparent mineralocorticoid excess."
Am. J. Hum. Genet. 63:370-379(1998) [PubMed] [Europe PMC] [Abstract]

"Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess."
J. Clin. Endocrinol. Metab. 83:2244-2254(1998) [PubMed] [Europe PMC] [Abstract]

"The codon 213 of the 11beta-hydroxysteroid dehydrogenase type 2 gene is a hot spot for mutations in apparent mineralocorticoid excess."
J. Clin. Endocrinol. Metab. 83:4391-4393(1998) [PubMed] [Europe PMC] [Abstract]

"A genetic defect resulting in mild low-renin hypertension."
Proc. Natl. Acad. Sci. U.S.A. 95:10200-10205(1998) [PubMed] [Europe PMC] [Abstract]

"Genetic, biochemical, and clinical studies of patients with A328V or R213C mutations in 11betaHSD2 causing apparent mineralocorticoid excess."
Hypertension 34:435-441(1999) [PubMed] [Europe PMC] [Abstract]

"Mutants of 11beta-hydroxysteroid dehydrogenase (11-HSD2) with partial activity: improved correlations between genotype and biochemical phenotype in apparent mineralocorticoid excess."
Hypertension 34:638-642(1999) [PubMed] [Europe PMC] [Abstract]

"A mutation in the cofactor-binding domain of 11beta-hydroxysteroid dehydrogenase type 2 associated with mineralocorticoid hypertension."
J. Clin. Endocrinol. Metab. 86:1247-1252(2001) [PubMed] [Europe PMC] [Abstract]

"Two homozygous mutations in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess."
J. Clin. Endocrinol. Metab. 88:2501-2507(2003) [PubMed] [Europe PMC] [Abstract]

"Impaired protein stability of 11beta-hydroxysteroid dehydrogenase type 2: a novel mechanism of apparent mineralocorticoid excess."
J. Am. Soc. Nephrol. 18:1262-1270(2007) [PubMed] [Europe PMC] [Abstract]