Hsd11b2

Summary

Gene Symbol: Hsd11b2
Description: hydroxysteroid 11-beta dehydrogenase 2
Alias: 11HSD2, corticosteroid 11-beta-dehydrogenase isozyme 2, 11-DH2, 11-beta-HSD2, 11-beta-hydroxysteroid dehydrogenase type 2, NAD-dependent 11-beta-hydroxysteroid dehydrogenase
Species: mouse
Products:     Hsd11b2

Top Publications

  1. Cole T. Cloning of the mouse 11 beta-hydroxysteroid dehydrogenase type 2 gene: tissue specific expression and localization in distal convoluted tubules and collecting ducts of the kidney. Endocrinology. 1995;136:4693-6 pubmed
    ..11 beta-HSD2 therefore appears to act in a protective role to exclude glucocorticoids from mineralocorticoid receptors in the kidney. ..
  2. O Brien C, Jia D, Plotkin L, Bellido T, Powers C, Stewart S, et al. Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology. 2004;145:1835-41 pubmed
    ..Furthermore, our results suggest that glucocorticoid-induced loss of bone strength results in part from increased death of osteocytes, independent of bone loss. ..
  3. Holmes M, Sangra M, French K, Whittle I, Paterson J, Mullins J, et al. 11beta-Hydroxysteroid dehydrogenase type 2 protects the neonatal cerebellum from deleterious effects of glucocorticoids. Neuroscience. 2006;137:865-73 pubmed
    ..We therefore suggest that 11beta-hydroxysteroid dehydrogenase type 2 acts as to protect the developing nervous system from the deleterious consequences of glucocorticoid overexposure. ..
  4. Bailey M, Craigie E, Livingstone D, Kotelevtsev Y, Al Dujaili E, Kenyon C, et al. Hsd11b2 haploinsufficiency in mice causes salt sensitivity of blood pressure. Hypertension. 2011;57:515-520 pubmed publisher
    ..Polymorphisms in HSD11B2 are associated with salt sensitivity of blood pressure in normotensives...
  5. Abbott A, Guidry T, Welsh K, Thomas A, Kling M, Hunter R, et al. 11beta-hydroxysteroid dehydrogenases are regulated during the pulmonary granulomatous response to the mycobacterial glycolipid trehalose-6,6'-dimycolate. Neuroimmunomodulation. 2009;16:147-54 pubmed publisher
  6. Wyrwoll C, Seckl J, Holmes M. Altered placental function of 11beta-hydroxysteroid dehydrogenase 2 knockout mice. Endocrinology. 2009;150:1287-93 pubmed publisher
    ..Our data suggest that restriction of fetal growth in 11beta-HSD2(-/-) mice is mediated, at least in part, via altered placental transport of nutrients and reduction in placental vascularization. ..
  7. Kotelevtsev Y, Brown R, Fleming S, Kenyon C, Edwards C, Seckl J, et al. Hypertension in mice lacking 11beta-hydroxysteroid dehydrogenase type 2. J Clin Invest. 1999;103:683-9 pubmed
    ..Thus, 11beta-HSD2(-/-) mice demonstrate the major features of SAME, providing a unique rodent model to study the molecular mechanisms of kidney resetting leading to hypertension. ..
  8. Holmes M, Kotelevtsev Y, Mullins J, Seckl J. Phenotypic analysis of mice bearing targeted deletions of 11beta-hydroxysteroid dehydrogenases 1 and 2 genes. Mol Cell Endocrinol. 2001;171:15-20 pubmed
    ..Overall, these transgenic models have proved very useful for elucidating the roles of 11beta-HSDs in vivo and will be a unique resource for investigating the importance of each enzyme in the diverse actions of glucocorticoids. ..
  9. Craigie E, Evans L, Mullins J, Bailey M. Failure to downregulate the epithelial sodium channel causes salt sensitivity in Hsd11b2 heterozygote mice. Hypertension. 2012;60:684-90 pubmed publisher
    ..Ablation of the encoding gene, HSD11B2, causes the hypertensive syndrome of apparent mineralocorticoid excess...

More Information

Publications53

  1. Holmes M, Abrahamsen C, French K, Paterson J, Mullins J, Seckl J. The mother or the fetus? 11beta-hydroxysteroid dehydrogenase type 2 null mice provide evidence for direct fetal programming of behavior by endogenous glucocorticoids. J Neurosci. 2006;26:3840-4 pubmed
    ..This provides clear evidence for the key role of fetoplacental 11beta-HSD2 in prenatal glucocorticoid programming. ..
  2. Martinerie L, Viengchareun S, Delezoide A, Jaubert F, Sinico M, Prevot S, et al. Low renal mineralocorticoid receptor expression at birth contributes to partial aldosterone resistance in neonates. Endocrinology. 2009;150:4414-24 pubmed publisher
    ..Elucidation of regulatory mechanisms governing MR expression should lead to new strategies for the management of sodium waste in preterms and neonates. ..
  3. Condon J, Ricketts M, Whorwood C, Stewart P. Ontogeny and sexual dimorphic expression of mouse type 2 11beta-hydroxysteroid dehydrogenase. Mol Cell Endocrinol. 1997;127:121-8 pubmed
  4. Thompson A, Han V, Yang K. Differential expression of 11beta-hydroxysteroid dehydrogenase types 1 and 2 mRNA and glucocorticoid receptor protein during mouse embryonic development. J Steroid Biochem Mol Biol. 2004;88:367-75 pubmed
  5. Gong R, Morris D, Brem A. Variable expression of 11beta Hydroxysteroid dehydrogenase (11beta-HSD) isoforms in vascular endothelial cells. Steroids. 2008;73:1187-96 pubmed publisher
    ..Changes in 11beta-HSD1 with growth and during repair occurred at the transcription level. Thus, 11beta-HSD1 protein expression predominates in endothelial cells and varies during periods of growth. ..
  6. Rossier B, Staub O, Hummler E. Genetic dissection of sodium and potassium transport along the aldosterone-sensitive distal nephron: importance in the control of blood pressure and hypertension. FEBS Lett. 2013;587:1929-41 pubmed publisher
    ..This will allow to design rational strategies for the treatment of hypertension and for the development of the next generation of diuretics. ..
  7. Deuchar G, McLean D, Hadoke P, Brownstein D, Webb D, Mullins J, et al. 11β-hydroxysteroid dehydrogenase type 2 deficiency accelerates atherogenesis and causes proinflammatory changes in the endothelium in apoe-/- mice. Endocrinology. 2011;152:236-246 pubmed publisher
    ..Thus, loss of 11β-HSD2 leads to striking atherogenesis associated with activation of MR, stimulating proinflammatory processes in the endothelium of E/b2 mice. ..
  8. Ueda K, Nishimoto M, Hirohama D, Ayuzawa N, Kawarazaki W, Watanabe A, et al. Renal Dysfunction Induced by Kidney-Specific Gene Deletion of Hsd11b2 as a Primary Cause of Salt-Dependent Hypertension. Hypertension. 2017;70:111-118 pubmed publisher
    ..sodium-transporting system has identified specific variations of Mendelian hypertensive disorders, including HSD11B2 gene variants in apparent mineralocorticoid excess...
  9. Umekawa T, Sugiyama T, Kihira T, Murabayashi N, Zhang L, Nagao K, et al. Overexpression of thioredoxin-1 reduces oxidative stress in the placenta of transgenic mice and promotes fetal growth via glucose metabolism. Endocrinology. 2008;149:3980-8 pubmed publisher
    ..In particular, increased hTRX-1 activity and the resulting modified placental redox state may play an important role in fetal growth by increasing the availability of glucose. ..
  10. Lavall D, Schuster P, Jacobs N, Kazakov A, Böhm M, Laufs U. Rac1 GTPase regulates 11β hydroxysteroid dehydrogenase type 2 and fibrotic remodeling. J Biol Chem. 2017;292:7542-7553 pubmed publisher
    ..In conclusion, Rac1 GTPase regulates 11β-HSD2 expression, MR activation, and MR-mediated pro-fibrotic signaling. ..
  11. Jensen Peña C, Monk C, Champagne F. Epigenetic effects of prenatal stress on 11?-hydroxysteroid dehydrogenase-2 in the placenta and fetal brain. PLoS ONE. 2012;7:e39791 pubmed publisher
    ..Placental 11?-hydroxysteroid dehydrogenase type 2 (HSD11B2) buffers the impact of maternal glucocorticoid exposure by converting cortisol/corticosterone into inactive ..
  12. Jiang L, Yang S, Yin H, Fan X, Wang S, Yao B, et al. Epithelial-specific deletion of 11?-HSD2 hinders Apcmin/+ mouse tumorigenesis. Mol Cancer Res. 2013;11:1040-50 pubmed publisher
    ..Inhibition of 11?-HSD2 may represent a novel approach for colorectal cancer chemoprevention by increasing tumor glucocorticoid activity, which in turn inhibits tumor growth by multiple pathways. ..
  13. Christy C, Hadoke P, Paterson J, Mullins J, Seckl J, Walker B. 11beta-hydroxysteroid dehydrogenase type 2 in mouse aorta: localization and influence on response to glucocorticoids. Hypertension. 2003;42:580-7 pubmed
    ..It has been suggested that 11HSD2 influences vascular function directly by limiting glucocorticoid-mediated inhibition of endothelium-derived nitric ..
  14. Chadwick J, Swager S, Lowe J, Welc S, Tidball J, Gomez Sanchez C, et al. Myeloid cells are capable of synthesizing aldosterone to exacerbate damage in muscular dystrophy. Hum Mol Genet. 2016;25:5167-5177 pubmed publisher
    ..This first report of myeloid cells having the capacity to produce aldosterone may have implications for a wide variety of acute injuries and chronic diseases with inflammation where MR antagonists may be therapeutic. ..
  15. Rog Zielinska E, Thomson A, Kenyon C, Brownstein D, Moran C, Szumska D, et al. Glucocorticoid receptor is required for foetal heart maturation. Hum Mol Genet. 2013;22:3269-82 pubmed publisher
  16. Martineau M, Papacleovoulou G, Abu Hayyeh S, Dixon P, Ji H, Powrie R, et al. Cholestatic pregnancy is associated with reduced placental 11?HSD2 expression. Placenta. 2014;35:37-43 pubmed publisher
    ..UDCA, the main bile acid used to treat cholestasis, did not reduce placental 11?HSD2 expression, further supporting its use in the management of ICP. ..
  17. Boucher E, Provost P, Tremblay Y. Ontogeny of adrenal-like glucocorticoid synthesis pathway and of 20?-hydroxysteroid dehydrogenase in the mouse lung. BMC Res Notes. 2014;7:119 pubmed publisher
    ..Glucocorticoids from lung 21-hydroxylase appear to modulate lung ontogenesis through paracrine/intracrine actions. ..
  18. Martinerie L, Pussard E, Meduri G, Delezoide A, Boileau P, Lombes M. Lack of renal 11 beta-hydroxysteroid dehydrogenase type 2 at birth, a targeted temporal window for neonatal glucocorticoid action in human and mice. PLoS ONE. 2012;7:e31949 pubmed publisher
  19. Chang J, Xue M, Yang S, Yao B, Zhang B, Chen X, et al. Inhibition of 11β-Hydroxysteroid Dehydrogenase Type II Suppresses Lung Carcinogenesis by Blocking Tumor COX-2 Expression as Well as the ERK and mTOR Signaling Pathways. PLoS ONE. 2015;10:e0127030 pubmed publisher
  20. Iqbal J, Macdonald L, Low L, Seckl J, Yau C, Walker B, et al. Contribution of endogenous glucocorticoids and their intravascular metabolism by 11β-HSDs to postangioplasty neointimal proliferation in mice. Endocrinology. 2012;153:5896-905 pubmed publisher
    ..Reducing glucocorticoid action with 11β-HSD1 inhibitors that are being developed for type 2 diabetes appears not to risk enhanced neointimal proliferation. ..
  21. Noguchi K, Lau K, Smith D, Swiney B, Farber N. Glucocorticoid receptor stimulation and the regulation of neonatal cerebellar neural progenitor cell apoptosis. Neurobiol Dis. 2011;43:356-63 pubmed publisher
    ..These results are discussed in terms of their implications for glucocorticoid therapy and neurodevelopment during the perinatal period. ..
  22. Thompson A, Han V, Yang K. Spatial and temporal patterns of expression of 11beta-hydroxysteroid dehydrogenase types 1 and 2 messenger RNA and glucocorticoid receptor protein in the murine placenta and uterus during late pregnancy. Biol Reprod. 2002;67:1708-18 pubmed
  23. Hadoke P, Christy C, Kotelevtsev Y, Williams B, Kenyon C, Seckl J, et al. Endothelial cell dysfunction in mice after transgenic knockout of type 2, but not type 1, 11beta-hydroxysteroid dehydrogenase. Circulation. 2001;104:2832-7 pubmed
    ..This appears to be independent of renal sodium retention and may contribute to hypertension in 11betaHSD2 deficiency. ..
  24. Yamaguchi H, Yu T, Noshita T, Kidachi Y, Kamiie K, Yoshida K, et al. Ligand-receptor interaction between triterpenoids and the 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) enzyme predicts their toxic effects against tumorigenic r/m HM-SFME-1 cells. J Biol Chem. 2011;286:36888-97 pubmed publisher
    ..To the best of our knowledge, this is the first report on in silico prediction of the toxic effects of triterpenoids on tumor cells by 11?HSD2 inhibition. ..
  25. Boix J, Carceller E, Sevilla L, Marcos Garcés V, Perez P. The mineralocorticoid receptor plays a transient role in mouse skin development. Exp Dermatol. 2016;25:69-71 pubmed publisher
  26. Evans L, Ivy J, Wyrwoll C, McNairn J, Menzies R, Christensen T, et al. Conditional Deletion of Hsd11b2 in the Brain Causes Salt Appetite and Hypertension. Circulation. 2016;133:1360-70 pubmed publisher
    ..We therefore used a Cre-Lox strategy to generate 11βHSD2 brain-specific knockout (Hsd11b2.BKO) mice, measuring blood pressure and salt appetite in adults...
  27. NARAY FEJES TOTH A, Fejes Toth G. Novel mouse strain with Cre recombinase in 11beta-hydroxysteroid dehydrogenase-2-expressing cells. Am J Physiol Renal Physiol. 2007;292:F486-94 pubmed
    ..Cre (iCre) recombinase (48) under the control of the endogenous 11beta-hydroxysteroid dehydrogenase type 2 (11HSD2) promoter...
  28. Ha T, Swanson D, Kirova R, Yeung J, Choi K, Tong Y, et al. Genome-wide microarray comparison reveals downstream genes of Pax6 in the developing mouse cerebellum. Eur J Neurosci. 2012;36:2888-98 pubmed publisher
    ..The candidate genes identified in this way represent direct or indirect Pax6-downstream genes involved in cerebellar development. ..
  29. Moore X, Hoong I, Cole T. Expression of the 11beta-hydroxysteroid dehydrogenase 2 gene in the mouse. Kidney Int. 2000;57:1307-12 pubmed
  30. Oppermann U, Persson B, Jornvall H. Function, gene organization and protein structures of 11beta-hydroxysteroid dehydrogenase isoforms. Eur J Biochem. 1997;249:355-60 pubmed
    ..On the other hand, for adrenal glucocorticoids the type-2 enzyme seems to be exclusively a dehydrogenase and, by inactivating glucocorticoids, confers specificity to peripheral mineralocorticoid receptors. ..
  31. Jarvie B, Palmiter R. HSD2 neurons in the hindbrain drive sodium appetite. Nat Neurosci. 2017;20:167-169 pubmed publisher
    ..These HSD2-positive neurons are necessary for full expression of sodium appetite and have distinct downstream targets that are activated during sodium depletion. ..
  32. Resch J, Fenselau H, Madara J, Wu C, Campbell J, Lyubetskaya A, et al. Aldosterone-Sensing Neurons in the NTS Exhibit State-Dependent Pacemaker Activity and Drive Sodium Appetite via Synergy with Angiotensin II Signaling. Neuron. 2017;96:190-206.e7 pubmed publisher
    ..The interaction between angiotensin signaling and NTSHSD2 neurons provides a neuronal context for the long-standing "synergy hypothesis" of sodium appetite regulation. ..
  33. Cuffe J, O Sullivan L, Simmons D, Anderson S, Moritz K. Maternal corticosterone exposure in the mouse has sex-specific effects on placental growth and mRNA expression. Endocrinology. 2012;153:5500-11 pubmed publisher
    ..Our study has shown that maternal Cort exposure infers a sex-specific alteration to normal placental growth and growth factor expression, thus further adding to our understanding of the mechanisms of male dominance of programmed disease...
  34. Evans L, Livingstone D, Kenyon C, Jansen M, Dear J, Mullins J, et al. A urine-concentrating defect in 11?-hydroxysteroid dehydrogenase type 2 null mice. Am J Physiol Renal Physiol. 2012;303:F494-502 pubmed publisher
    ..Null mutations in the encoding gene, HSD11B2, cause apparent mineralocorticoid excess, in which hypertension is thought to reflect volume expansion secondary ..
  35. Coutinho A, Gray M, Brownstein D, Salter D, Sawatzky D, Clay S, et al. 11?-Hydroxysteroid dehydrogenase type 1, but not type 2, deficiency worsens acute inflammation and experimental arthritis in mice. Endocrinology. 2012;153:234-40 pubmed publisher
    ..In contrast, 11?-HSD2 plays no role in acute inflammatory responses in mice. Regulation of local 11?-HSD1 expression and/or delivery of substrate may afford a novel approach for antiinflammatory therapy. ..
  36. Heine V, Rowitch D. Hedgehog signaling has a protective effect in glucocorticoid-induced mouse neonatal brain injury through an 11betaHSD2-dependent mechanism. J Clin Invest. 2009;119:267-77 pubmed publisher
    ..Furthermore, they led us to propose that 11betaHSD2-sensitive GCs (e.g., hydrocortisone) should be used in preference to dexamethasone in neonatal human infants because of the potential for reduced neurotoxicity. ..
  37. Bailey M, Paterson J, Hadoke P, Wrobel N, Bellamy C, Brownstein D, et al. A switch in the mechanism of hypertension in the syndrome of apparent mineralocorticoid excess. J Am Soc Nephrol. 2008;19:47-58 pubmed
    ..In summary, it is proposed that renal sodium retention remains a key event in apparent mineralocorticoid excess but that the accompanying hypertension changes from a renal to a vascular etiology over time. ..
  38. Li K, Smith R, Ferrari P, Funder J, Krozowski Z. Rat 11 beta-hydroxysteroid dehydrogenase type 2 enzyme is expressed at low levels in the placenta and is modulated by adrenal steroids in the kidney. Mol Cell Endocrinol. 1996;120:67-75 pubmed
    The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) protects the non-discriminating mineralocorticoid receptor from occupation by glucocorticoids...
  39. 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. ..
  40. Terao M, Itoi S, Murota H, Katayama I. Expression profiles of cortisol-inactivating enzyme, 11?-hydroxysteroid dehydrogenase-2, in human epidermal tumors and its role in keratinocyte proliferation. Exp Dermatol. 2013;22:98-101 pubmed publisher
    ..Assessing 11?-HSD1 and 11?-HSD2 expression could be a useful tool for diagnosing and characterizing skin tumors...
  41. Liang G, Chen M, Pan X, Zheng J, Wang H. Ethanol-induced inhibition of fetal hypothalamic-pituitary-adrenal axis due to prenatal overexposure to maternal glucocorticoid in mice. Exp Toxicol Pathol. 2011;63:607-11 pubmed publisher
  42. Yang M, Trettel L, Adams D, Harrison J, Canalis E, Kream B. Col3.6-HSD2 transgenic mice: a glucocorticoid loss-of-function model spanning early and late osteoblast differentiation. Bone. 2010;47:573-82 pubmed publisher
    ..These data further strengthen the concept that endogenous glucocorticoid signaling is required for optimal bone mass acquisition and highlight the complexities of glucocorticoid signaling in bone cell lineages. ..
  43. Huang Y, Li X, Lin H, Chu Y, Chen B, Lian Q, et al. Regulation of 11beta-hydroxysteroid dehydrogenase 1 and 2 by IGF-1 in mice. Biochem Biophys Res Commun. 2010;391:1752-6 pubmed publisher
    ..The regulation of 11beta-HSD1 and 11beta-HSD2 mRNA (Hsd11b1 and Hsd11b2) levels and their activities by IGF-1 was performed in liver, kidney, and testis of IGF-1 knockout male mice...
  44. Campbell L, Yu M, Yang K. Ovine 11 beta-hydroxysteroid dehydrogenase type 2 gene predicts a protein distinct from that deduced by the cloned kidney cDNA at the C-terminus. Mol Cell Endocrinol. 1996;119:113-8 pubmed
    ..The cloning of the sheep 11 beta-HSD2 gene should facilitate future studies on the regulation of 11 beta-HSD2 gene expression during fetal development in a mammalian model. ..