Genomes and Genes
Gene Symbol: Hsd11b2
Description: hydroxysteroid 11-beta dehydrogenase 2
Alias: corticosteroid 11-beta-dehydrogenase isozyme 2, 11-DH2, 11-beta-HSD2, 11-beta-hydroxysteroid dehydrogenase type 2, Hydroxysteroid dehydrogenase, 11 beta type 2, NAD-dependent 11-beta-hydroxysteroid dehydrogenase
- Lavery G, McTernan C, Bain S, Chowdhury T, Hewison M, Stewart P. Association studies between the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2), type 1 diabetes mellitus and diabetic nephropathy. Eur J Endocrinol. 2002;146:553-8 pubmedMutations in the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2) explain the syndrome of apparent mineralocorticoid excess where cortisol acts as a mineralocorticoid...
- Xu Z, Zhao J, Zhang H, Ke T, Xu P, Cai W, et al. Spontaneous miscarriages are explained by the stress/glucocorticoid/lipoxin A4 axis. J Immunol. 2013;190:6051-8 pubmed publisher..Together, these findings suggest that the stress/glucocorticoid/LXA4 axis might be a common pathway through which miscarriages occur. ..
- Takaya J, Iharada A, Okihana H, Kaneko K. Magnesium deficiency in pregnant rats alters methylation of specific cytosines in the hepatic hydroxysteroid dehydrogenase-2 promoter of the offspring. Epigenetics. 2011;6:573-8 pubmed..receptor ? (Ppara), glucocorticoid receptor (Nr3c1) and 11?-hydroxysteroid dehydrogenase-2 (Hsd11b2) promoters in the liver were measured by pyrosequencing...
- Nørregaard R, Uhrenholt T, Bistrup C, Skøtt O, Jensen B. Stimulation of 11-beta-hydroxysteroid dehydrogenase type 2 in rat colon but not in kidney by low dietary NaCl intake. Am J Physiol Renal Physiol. 2003;285:F348-58 pubmed..These data indicate that mineralocorticoid selectivity is physiologically regulated by NaCl intake at the level of 11betaHSD-2 expression and tissue distribution in the distal colon, but not in the kidney. ..
- Li A, Tedde R, Krozowski Z, Pala A, Li K, Shackleton C, et al. Molecular basis for hypertension in the "type II variant" of apparent mineralocorticoid excess. Am J Hum Genet. 1998;63:370-9 pubmed..Hypertensive populations should be screened to identify the prevalence of milder defects in 11beta-HSD2 in patients currently labeled as having "essential" hypertension. ..
- Kim S, Schou U, Peters C, de Seigneux S, Kwon T, Knepper M, et al. Increased apical targeting of renal epithelial sodium channel subunits and decreased expression of type 2 11beta-hydroxysteroid dehydrogenase in rats with CCl4-induced decompensated liver cirrhosis. J Am Soc Nephrol. 2005;16:3196-210 pubmed..In conclusion, increased apical targeting of ENaC subunits combined with diminished abundance of 11betaHSD2 in the DCT2, CNT, and cortical collecting duct is likely to play a role in the sodium retaining stage of liver cirrhosis. ..
- Milagro F, Campion J, Martinez J. 11-Beta hydroxysteroid dehydrogenase type 2 expression in white adipose tissue is strongly correlated with adiposity. J Steroid Biochem Mol Biol. 2007;104:81-4 pubmed..Thus, 11betaHSD2 is expressed in adipose tissue by both adipocytes and stromal-vascular cells, which suggests that this enzyme may play an important role in preventing fat accumulation in adipose tissue. ..
- Ge R, Dong Q, Sottas C, Latif S, Morris D, Hardy M. Stimulation of testosterone production in rat Leydig cells by aldosterone is mineralocorticoid receptor mediated. Mol Cell Endocrinol. 2005;243:35-42 pubmed..We conclude that Leydig cells express MRs and that testosterone production is subject to regulation by aldosterone. ..
- Li L, Wu X, Guan H, Mao B, Wang H, Yuan X, et al. Zearalenone Inhibits Rat and Human 11Î²-Hydroxysteroid Dehydrogenase Type 2. Biomed Res Int. 2015;2015:283530 pubmed publisher..11Î²-Hydroxysteroid dehydrogenases, isoforms 1 (HSD11B1) and 2 (HSD11B2), have been demonstrated to be the regulators of the local level of active glucocorticoid, which has a broad ..
- Ma S, Nam K, Kim S, Bae E, Choi K, Lee J. Increased renal expression of aquaporin-3 in rats inhibited type 2 11beta-hydroxysteroid dehydrogenase. Kidney Blood Press Res. 2007;30:8-14 pubmed..A decreased expression of 11betaHSD2 may result in an upregulation of AQP3, in which AVP/cAMP-dependent mechanisms are unlikely to be involved. ..
- Baserga M, Hale M, Wang Z, Yu X, Callaway C, McKnight R, et al. Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension. Am J Physiol Regul Integr Comp Physiol. 2007;292:R1943-55 pubmed..We conclude that in our animal model, UPI decreases fetal COX-2 expression during a period of active nephrogenesis in the IUGR rat, which is also characterized by decreased nephron number and adult-onset hypertension. ..
- Sheppard K, Autelitano D. 11Beta-hydroxysteroid dehydrogenase 1 transforms 11-dehydrocorticosterone into transcriptionally active glucocorticoid in neonatal rat heart. Endocrinology. 2002;143:198-204 pubmed
- Koeva Y, Bakalska M, Atanassova N, Georgieva K, Davidoff M. Age-related changes in the expression of 11beta-hydroxysteroid dehydrogenase type 2 in rat Leydig cells. Folia Histochem Cytobiol. 2009;47:281-7 pubmed publisher..The observed reduction in 11beta-HSD type 2 expression in aging LCs reflects the decline in their protection ability, opposing the suppressive effect of glucocorticoids on testosterone production. ..
- Audigé A, Dick B, Frey B, Frey F, Corman B, Vogt B. Glucocorticoids and 11 beta-hydroxysteroid dehydrogenase type 2 gene expression in the aging kidney. Eur J Clin Invest. 2002;32:411-20 pubmed
- Rezaei M, Andrieu T, Neuenschwander S, Bruggmann R, Mordasini D, Frey F, et al. Regulation of 11?-hydroxysteroid dehydrogenase type 2 by microRNA. Hypertension. 2014;64:860-6 pubmed publisher..The mechanism of the variable and distinct 11?-hydroxysteroid dehydrogenase type 2 gene (HSD11B2) expression in the cortical collecting duct is poorly understood...
- Lavall D, Schuster P, Jacobs N, Kazakov A, BÃ¶hm M, Laufs U. Rac1 GTPase regulates 11Î² hydroxysteroid dehydrogenase type 2 and fibrotic remodeling. J Biol Chem. 2017;292:7542-7553 pubmed publisher..In conclusion, Rac1 GTPase regulates 11Î²-HSD2 expression, MR activation, and MR-mediated pro-fibrotic signaling. ..
- Kim S, de Seigneux S, Sassen M, Lee J, Kim J, Knepper M, et al. Increased apical targeting of renal ENaC subunits and decreased expression of 11betaHSD2 in HgCl2-induced nephrotic syndrome in rats. Am J Physiol Renal Physiol. 2006;290:F674-87 pubmed..The decreased abundance of NHE3, NKCC2, NCC, and Na-K-ATPase may play a compensatory role in promoting sodium excretion. ..
- Yao B, Harris R, Zhang M. Interactions between 11beta-hydroxysteroid dehydrogenase and COX-2 in kidney. Am J Physiol Regul Integr Comp Physiol. 2005;288:R1767-73 pubmed
- Alikhani Koopaei R, Fouladkou F, Frey F, Frey B. Epigenetic regulation of 11 beta-hydroxysteroid dehydrogenase type 2 expression. J Clin Invest. 2004;114:1146-57 pubmedThe enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) is selectively expressed in aldosterone target tissues, where it confers aldosterone selectivity for the mineralocorticoid receptor by inactivating 11 beta-..
- Mazancova K, Kopecky M, Miksik I, Pacha J. 11beta-Hydroxysteroid dehydrogenase in the heart of normotensive and hypertensive rats. J Steroid Biochem Mol Biol. 2005;94:273-7 pubmed..These results show that the heart is able to metabolize glucocorticoids and that this metabolism is strain-dependent but do not support the notion of association between cardiac hypertrophy and changes of 11HSD1 and 11HSD2 expression...
- Konishi A, Tazawa C, Miki Y, Darnel A, Suzuki T, Ohta Y, et al. The possible roles of mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type 2 in cardiac fibrosis in the spontaneously hypertensive rat. J Steroid Biochem Mol Biol. 2003;85:439-42 pubmed..Findings from the present study appear to demonstrate that MR and 11beta-HSD2 mRNA significantly rise in the left ventricle of M-SHRSP and increase of these mRNA is one of the cause of cardiac fibrosis. ..
- Vagnerova K, Vackova Z, Klusonova P, Staud F, Kopecky M, Ergang P, et al. Reciprocal changes in maternal and fetal metabolism of corticosterone in rat during gestation. Reprod Sci. 2008;15:921-31 pubmed publisher..The final third of gestation is accompanied by reciprocal changes in placental and fetal metabolism of corticosterone due to changes in 11HSD1 and 11HSD2 not only at the level of transcription but also at a posttranslational level. ..
- Pacha J, Lisa V, Miksik I. Effect of cellular differentiation on 11beta-hydroxysteroid dehydrogenase activity in the intestine. Steroids. 2002;67:119-26 pubmed
- Balazs Z, Schweizer R, Frey F, Rohner Jeanrenaud F, Odermatt A. DHEA induces 11 -HSD2 by acting on CCAAT/enhancer-binding proteins. J Am Soc Nephrol. 2008;19:92-101 pubmed..It was found that CCAAT/enhancer-binding protein-alpha (C/EBP-alpha) and C/EBP-beta regulated HSD11B2 transcription and that DHEA likely modulated the transcription of 11beta-HSD2 in a phosphatidylinositol-3 kinase/..
- Chen M, Wang T, Liao Z, Pan X, Feng Y, Wang H. Nicotine-induced prenatal overexposure to maternal glucocorticoid and intrauterine growth retardation in rat. Exp Toxicol Pathol. 2007;59:245-51 pubmed
- Klusonova P, Rehakova L, Borchert G, Vagnerova K, Neckar J, Ergang P, et al. Chronic intermittent hypoxia induces 11beta-hydroxysteroid dehydrogenase in rat heart. Endocrinology. 2009;150:4270-7 pubmed publisher..These findings suggest that myocardial remodeling induced by CIH is associated with the up-regulation of cardiac 11HSD2. Consequently, local metabolism of glucocorticoids could indeed play a role in cardiac hypertrophy and fibrosis. ..
- Koeva Y, Bakalska M, Atanassova N, Georgieva K, Davidoff M. 11beta-hydroxysteroid dehydrogenase type 2 expression in the newly formed Leydig cells after ethane dimethanesulphonate treatment of adult rats. Folia Histochem Cytobiol. 2007;45:381-6 pubmed
- Geerling J, Loewy A. Sodium deprivation and salt intake activate separate neuronal subpopulations in the nucleus of the solitary tract and the parabrachial complex. J Comp Neurol. 2007;504:379-403 pubmed..These findings offer new perspectives on the roles of sensory information from the brainstem in the regulation of sodium appetite. ..
- Takeda M, Tatsumi T, Matsunaga S, Hayashi H, Kimata M, Honsho S, et al. Spironolactone modulates expressions of cardiac mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase 2 and prevents ventricular remodeling in post-infarct rat hearts. Hypertens Res. 2007;30:427-37 pubmed
- Jang C, Obeyesekere V, Dilley R, Krozowski Z, Inder W, Alford F. Altered activity of 11beta-hydroxysteroid dehydrogenase types 1 and 2 in skeletal muscle confers metabolic protection in subjects with type 2 diabetes. J Clin Endocrinol Metab. 2007;92:3314-20 pubmed..463; P = 0.026). The activities of skeletal muscle 11beta-HSD1 and 11beta-HSD2 are altered in diabetes, which together may reduce intracellular cortisol generation, potentially conferring metabolic protection. ..
- Liu Y, Nakagawa Y, Toya K, Wang Y, Saegusa H, Nakanishi T, et al. Effects of spironolactone on systolic blood pressure in experimental diabetic rats. Kidney Int. 2000;57:2064-71 pubmed
- Kershaw E, Morton N, Dhillon H, Ramage L, Seckl J, Flier J. Adipocyte-specific glucocorticoid inactivation protects against diet-induced obesity. Diabetes. 2005;54:1023-31 pubmed..These data suggest that reduction of active GCs exclusively in adipose tissue is an important determinant of a favorable metabolic phenotype with respect to energy homeostasis and the metabolic syndrome. ..
- Remer T, Maser Gluth C, Boye K, Hartmann M, Heinze E, Wudy S. Exaggerated adrenarche and altered cortisol metabolism in Type 1 diabetic children. Steroids. 2006;71:591-8 pubmed..Whether the elevated urinary 6beta-hydroxycortisol and cortisone excretion, observed in the patients, are also present in other forms of hypercortisolism and may thus serve as non-invasive clinical stress markers deserves further study. ..
- Lauterburg M, Escher G, Dick B, Ackermann D, Frey F. Uninephrectomy reduces 11?-hydroxysteroid dehydrogenase type 1 and type 2 concomitantly with an increase in blood pressure in rats. J Endocrinol. 2012;214:373-80 pubmed publisher..Both 11?-HSD1 and 11?-HSD2 are downregulated after UNX in rats, a constellation considered to induce hypertension. ..
- Wang Y, Wu J, Tian S, Li S, Gu Q. [Roles of type II 11Î²-hydroxysteroid dehydrogenase and its signaling factors in pathogenesis of persistent pulmonary hypertension in neonatal rats]. Zhongguo Dang Dai Er Ke Za Zhi. 2014;16:939-43 pubmed..05). 11Î²-HSD2 and it's signaling factors play roles in pathogenesis of PPH in neonatal rats. ..
- Zhou M, Gomez Sanchez E, Cox D, Cosby D, Gomez Sanchez C. Cloning, expression, and tissue distribution of the rat nicotinamide adenine dinucleotide-dependent 11 beta-hydroxysteroid dehydrogenase. Endocrinology. 1995;136:3729-34 pubmed..1 +/- 2.1 nM. In conclusion, we have cloned a rat NAD(+)-dependent 11 beta HSD with tissue distribution and kinetic characteristics suggesting that it could play a significant role in mineralocorticoid receptor selectivity. ..
- Lucassen P, Bosch O, Jousma E, Krömer S, Andrew R, Seckl J, et al. Prenatal stress reduces postnatal neurogenesis in rats selectively bred for high, but not low, anxiety: possible key role of placental 11beta-hydroxysteroid dehydrogenase type 2. Eur J Neurosci. 2009;29:97-103 pubmed publisher..Hence, stress-induced placental 11beta-HSD2 expression may be critical in protecting the fetal brain from maternal stress-induced effects on adult neurogenesis. ..
- Liu Y, Mladinov D, Pietrusz J, Usa K, Liang M. Glucocorticoid response elements and 11 beta-hydroxysteroid dehydrogenases in the regulation of endothelial nitric oxide synthase expression. Cardiovasc Res. 2009;81:140-7 pubmed publisher..We identified the first GRE in the eNOS promoter region and demonstrated that endogenous 11 beta-HSD1 and 11 beta-HSD2 play significant and distinct roles in modulating the effect of glucocorticoids on eNOS expression. ..
- Li C, Wang W, Norregaard R, Knepper M, Nielsen S, Frøkiaer J. Altered expression of epithelial sodium channel in rats with bilateral or unilateral ureteral obstruction. Am J Physiol Renal Physiol. 2007;293:F333-41 pubmed..These results suggest that altered expression of alpha-, beta-, and gamma-ENaC may contribute to impaired renal sodium and water handling in response to ureteral obstruction. ..
- Groyer G, Eychenne B, Girard C, Rajkowski K, Schumacher M, Cadepond F. Expression and functional state of the corticosteroid receptors and 11 beta-hydroxysteroid dehydrogenase type 2 in Schwann cells. Endocrinology. 2006;147:4339-50 pubmed..These data support a physiological role for HSD2 regulation of glucocorticosteroid concentrations in nerve SC. ..
- Geerling J, Kawata M, Loewy A. Aldosterone-sensitive neurons in the rat central nervous system. J Comp Neurol. 2006;494:515-27 pubmed..The HSD2 neurons in the NTS may represent an important target for aldosterone action in the brain. ..
- Zallocchi M, Matkovic L, Calvo J, Damasco M. Adrenal gland involvement in the regulation of renal 11beta-hydroxysteroid dehydrogenase 2. J Cell Biochem. 2004;92:591-602 pubmed
- Waddell B, Hisheh S, Krozowski Z, Burton P. Localization of 11beta-hydroxysteroid dehydrogenase types 1 and 2 in the male reproductive tract. Endocrinology. 2003;144:3101-6 pubmed
- Zhao B, Lian Q, Chu Y, Hardy D, Li X, Ge R. The inhibition of human and rat 11?-hydroxysteroid dehydrogenase 2 by perfluoroalkylated substances. J Steroid Biochem Mol Biol. 2011;125:143-7 pubmed publisher..PFASs showed competitive inhibition of both human and rat 11?-HSD2 activities. This observation indicates that PFOS is a potent endocrine disruptor for glucocorticoid metabolism. Article from the Special issue on Targeted Inhibitors. ..
- Gomez Sanchez E, Ganjam V, Chen Y, Liu Y, Zhou M, Toroslu C, et al. Regulation of 11 beta-hydroxysteroid dehydrogenase enzymes in the rat kidney by estradiol. Am J Physiol Endocrinol Metab. 2003;285:E272-9 pubmed..NAD+-dependent enzymatic activity in the absence or presence of a reducing agent demonstrated that the increase in 11betaHSD2 protein was not associated with an increase in in vitro activity unless the dimers were reduced to monomers. ..
- Straley M, Togher K, Nolan A, Kenny L, O Keeffe G. LPS alters placental inflammatory and endocrine mediators and inhibits fetal neurite growth in affected offspring during late gestation. Placenta. 2014;35:533-8 pubmed publisher..at later gestational ages significantly increased pro-inflammatory IL-1? expression and reduced placental HSD11B2 expression...
- Haque M, Wilson R, Sharma K, Mills N, Teruyama R. Localisation of 11Î²-Hydroxysteroid Dehydrogenase Type 2 in Mineralocorticoid Receptor Expressing Magnocellular Neurosecretory Neurones of the Rat Supraoptic and Paraventricular Nuclei. J Neuroendocrinol. 2015;27:835-49 pubmed publisher..These findings strongly suggest that MNCs in the SON and PVN are aldosterone-sensitive neurones. ..
- Liu Y, Nakagawa Y, Ohzeki T. Gene expression of 11beta-hydroxysteroid dehydrogenase type 1 and type 2 in the kidneys of insulin-dependent diabetic rats. Hypertension. 1998;31:885-9 pubmed..These results indicate that alteration of renal 11beta-HSD2 activity and gene expression may be primarily responsible for the changes in blood pressure of STZ-diabetic rats after early treatment with insulin. ..
- Sato S, Fukushima K, Naito H, Funayama Y, Suzuki T, Sasano H, et al. Induction of 11beta-hydroxysteroid dehydrogenase type 2 and hyperaldosteronism are essential for enhanced sodium absorption after total colectomy in rats. Surgery. 2005;137:75-84 pubmed..Induction of 11beta-HSD 2 is essential for enhanced mineralocorticoid action in the remnant ileum after total colectomy in rats. ..
- Schmid J, Ludwig B, Schally A, Steffen A, Ziegler C, Block N, et al. Modulation of pancreatic islets-stress axis by hypothalamic releasing hormones and 11beta-hydroxysteroid dehydrogenase. Proc Natl Acad Sci U S A. 2011;108:13722-7 pubmed publisher..Agonists of CRHR1 and GHRH-receptor, therefore, may play an important role as novel therapeutic tools in the treatment of diabetes mellitus. ..