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Gene Review

HSD11B2  -  hydroxysteroid (11-beta) dehydrogenase 2

Homo sapiens

Synonyms: -HSD11 type II, 11-DH2, 11-beta-HSD, 11-beta-HSD2, 11-beta-hydroxysteroid dehydrogenase type 2, ...
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Disease relevance of HSD11B2


Psychiatry related information on HSD11B2

  • Comparison with previous enzymology studies suggest the changing pattern of 11 beta-HSD2 mRNA is likely to be translated into enzyme activity and have significant parallels in human development [6].
  • Clinical and autopsy studies of 14 patients treated with amphotericin B methyl ester (AME) for focal, disseminated, and nervous system mycotic infections revealed a high incidence of progressive neurologic dysfunction (dementia, akinesia, mutism, hyperreflexia, and tremor) and diffuse white matter degeneration [7].

High impact information on HSD11B2

  • The syndrome of AME is a rare form of juvenile hypertension in which 11-HSD is defective [8].
  • CpG islands covering the promoter and exon 1 of HSD11B2 were found to be densely methylated in tissues and cell lines with low expression but not those with high expression of HSD11B2 [1].
  • Methylation of HSD11B2 promoter-luciferase constructs decreased transcriptional activity [1].
  • Herein NF1 was identified as a strong HSD11B2 stimulatory factor [1].
  • The 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-hydroxyglucocorticoids [1].

Chemical compound and disease context of HSD11B2


Biological context of HSD11B2


Anatomical context of HSD11B2


Associations of HSD11B2 with chemical compounds

  • In 1995, it was shown that mutations in the gene (HSD11B2) encoding the 11beta-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2) cause AME [20].
  • Molecular analysis of the HSD11B2 gene of this patient showed a homozygous C-->T transition in the second nucleotide of codon 227, resulting in a substitution of proline with leucine (P227L) [20].
  • Approximately 5% conversion of cortisol to cortisone is predicted in subjects with mutations that completely inactivate HSD11B2, suggesting that a low level of enzymatic activity is mediated by another enzyme, possibly 11-HSD1 [21].
  • This suggest that some essential hypertensives, with suppressed renin activity, may have an impairment in the cortisol inactivation catalyzed by the enzyme 11betaHSD2, whose low activity in LREH patients could be associated with the length of CA-repeat microsatellite in intron 1 of the HSD11B2 gene [22].
  • Furthermore, cadmium diminished HSD11B2 promoter activity, indicative of repression of HSD11B2 gene transcription [23].

Physical interactions of HSD11B2


Co-localisations of HSD11B2


Regulatory relationships of HSD11B2


Other interactions of HSD11B2


Analytical, diagnostic and therapeutic context of HSD11B2


  1. Epigenetic regulation of 11 beta-hydroxysteroid dehydrogenase type 2 expression. Alikhani-Koopaei, R., Fouladkou, F., Frey, F.J., Frey, B.M. J. Clin. Invest. (2004) [Pubmed]
  2. Role of local 11 beta-hydroxysteroid dehydrogenase type 2 expression in determining the phenotype of adrenal adenomas. Mune, T., Morita, H., Suzuki, T., Takahashi, Y., Isomura, Y., Tanahashi, T., Daido, H., Yamakita, N., Deguchi, T., Sasano, H., White, P.C., Yasuda, K. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  3. Hypertension and the cortisol-cortisone shuttle. Quinkler, M., Stewart, P.M. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  4. A new polymorphic restriction site in the human 11 beta-hydroxysteroid dehydrogenase type 2 gene. Smolenicka, Z., Bach, E., Schaer, A., Liechti-Gallati, S., Frey, B.M., Frey, F.J., Ferrari, P. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  5. Association studies between the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2), type 1 diabetes mellitus and diabetic nephropathy. Lavery, G.G., McTernan, C.L., Bain, S.C., Chowdhury, T.A., Hewison, M., Stewart, P.M. Eur. J. Endocrinol. (2002) [Pubmed]
  6. The ontogeny of 11 beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor gene expression reveal intricate control of glucocorticoid action in development. Brown, R.W., Diaz, R., Robson, A.C., Kotelevtsev, Y.V., Mullins, J.J., Kaufman, M.H., Seckl, J.R. Endocrinology (1996) [Pubmed]
  7. Leukoencephalopathy in patients treated with amphotericin B methyl ester. Ellis, W.G., Sobel, R.A., Nielsen, S.L. J. Infect. Dis. (1982) [Pubmed]
  8. 11 beta-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess. White, P.C., Mune, T., Agarwal, A.K. Endocr. Rev. (1997) [Pubmed]
  9. Hypertension in the syndrome of apparent mineralocorticoid excess due to mutation of the 11 beta-hydroxysteroid dehydrogenase type 2 gene. Stewart, P.M., Krozowski, Z.S., Gupta, A., Milford, D.V., Howie, A.J., Sheppard, M.C., Whorwood, C.B. Lancet (1996) [Pubmed]
  10. Prenatal glucocorticoid exposure leads to offspring hyperglycaemia in the rat: studies with the 11 beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone. Lindsay, R.S., Lindsay, R.M., Waddell, B.J., Seckl, J.R. Diabetologia (1996) [Pubmed]
  11. Human 11 beta-hydroxysteroid dehydrogenase: studies on the stably transfected isoforms and localization of the type 2 isozyme within renal tissue. Bujalska, I., Shimojo, M., Howie, A., Stewart, P.M. Steroids (1997) [Pubmed]
  12. 11 beta-Hydroxysteroid dehydrogenases: key enzymes in determining tissue-specific glucocorticoid effects. Edwards, C.R., Benediktsson, R., Lindsay, R.S., Seckl, J.R. Steroids (1996) [Pubmed]
  13. In vivo footprinting of the human 11beta-hydroxysteroid dehydrogenase type 2 promoter: evidence for cell-specific regulation by Sp1 and Sp3. Nawrocki, A.R., Goldring, C.E., Kostadinova, R.M., Frey, F.J., Frey, B.M. J. Biol. Chem. (2002) [Pubmed]
  14. Genetic association of 11 beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) flanking microsatellites with essential hypertension in blacks. Watson, B., Bergman, S.M., Myracle, A., Callen, D.F., Acton, R.T., Warnock, D.G. Hypertension (1996) [Pubmed]
  15. Two homozygous mutations in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess. Carvajal, C.A., Gonzalez, A.A., Romero, D.G., González, A., Mosso, L.M., Lagos, E.T., Hevia, M.d.e.l. .P., Rosati, M.P., Perez-Acle, T.O., Gomez-Sanchez, C.E., Montero, J.A., Fardella, C.E. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  16. Peroxisome proliferator-activated receptor delta suppresses 11beta-hydroxysteroid dehydrogenase type 2 gene expression in human placental trophoblast cells. Julan, L., Guan, H., van Beek, J.P., Yang, K. Endocrinology (2005) [Pubmed]
  17. Point mutations abolish 11 beta-hydroxysteroid dehydrogenase type II activity in three families with the congenital syndrome of apparent mineralocorticoid excess. Ferrari, P., Obeyesekere, V.R., Li, K., Wilson, R.C., New, M.I., Funder, J.W., Krozowski, Z.S. Mol. Cell. Endocrinol. (1996) [Pubmed]
  18. 11 beta-Hydroxysteroid dehydrogenase type II in the human endometrium: localization and activity during the menstrual cycle. Smith, R.E., Salamonsen, L.A., Komesaroff, P.A., Li, K.X., Myles, K.M., Lawrence, M., Krozowski, Z. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  19. Immunodetection of 11 beta-hydroxysteroid dehydrogenase type 2 in human mineralocorticoid target tissues: evidence for nuclear localization. Shimojo, M., Ricketts, M.L., Petrelli, M.D., Moradi, P., Johnson, G.D., Bradwell, A.R., Hewison, M., Howie, A.J., Stewart, P.M. Endocrinology (1997) [Pubmed]
  20. A genetic defect resulting in mild low-renin hypertension. Wilson, R.C., Dave-Sharma, S., Wei, J.Q., Obeyesekere, V.R., Li, K., Ferrari, P., Krozowski, Z.S., Shackleton, C.H., Bradlow, L., Wiens, T., New, M.I. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  21. Mutants of 11beta-hydroxysteroid dehydrogenase (11-HSD2) with partial activity: improved correlations between genotype and biochemical phenotype in apparent mineralocorticoid excess. Nunez, B.S., Rogerson, F.M., Mune, T., Igarashi, Y., Nakagawa, Y., Phillipov, G., Moudgil, A., Travis, L.B., Palermo, M., Shackleton, C., White, P.C. Hypertension (1999) [Pubmed]
  22. Biochemical and genetic characterization of 11 beta-hydroxysteroid dehydrogenase type 2 in low-renin essential hypertensives. Carvajal, C.A., Romero, D.G., Mosso, L.M., González, A.A., Campino, C., Montero, J., Fardella, C.E. J. Hypertens. (2005) [Pubmed]
  23. Cadmium reduces 11 beta-hydroxysteroid dehydrogenase type 2 activity and expression in human placental trophoblast cells. Yang, K., Julan, L., Rubio, F., Sharma, A., Guan, H. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  24. Reduction of glucocorticoid receptor ligand binding by the 11-beta hydroxysteroid dehydrogenase type 2 inhibitor, Thiram. Garbrecht, M.R., Krozowski, Z.S., Snyder, J.M., Schmidt, T.J. Steroids (2006) [Pubmed]
  25. Immunohistochemical localization of the 11 beta-hydroxysteroid dehydrogenase type II enzyme in human kidney and placenta. Krozowski, Z., MaGuire, J.A., Stein-Oakley, A.N., Dowling, J., Smith, R.E., Andrews, R.K. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  26. Chenodeoxycholic acid and deoxycholic acid inhibit 11 beta-hydroxysteroid dehydrogenase type 2 and cause cortisol-induced transcriptional activation of the mineralocorticoid receptor. Stauffer, A.T., Rochat, M.K., Dick, B., Frey, F.J., Odermatt, A. J. Biol. Chem. (2002) [Pubmed]
  27. Expression of 11 beta-hydroxysteroid dehydrogenase isoenzymes in the human pituitary: induction of the type 2 enzyme in corticotropinomas and other pituitary tumors. Korbonits, M., Bujalska, I., Shimojo, M., Nobes, J., Jordan, S., Grossman, A.B., Stewart, P.M. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  28. Type 2 11 beta-hydroxysteroid dehydrogenase in foetal and adult life. Stewart, P.M., Whorwood, C.B., Mason, J.I. J. Steroid Biochem. Mol. Biol. (1995) [Pubmed]
  29. Growth hormone replacement inhibits renal and hepatic 11 beta-hydroxysteroid dehydrogenases in ACTH-deficient patients. Walker, B.R., Andrew, R., MacLeod, K.M., Padfield, P.L. Clin. Endocrinol. (Oxf) (1998) [Pubmed]
  30. c-Met expression in a gastric cancer cell line producing alpha-fetoprotein. Amemiya, H., Kono, K., Takahashi, A., Kamei, S., Sugai, H., Ichihara, F., Fujii, H., Matsumoto, Y. Surgery today. (2004) [Pubmed]
  31. A new compound heterozygous mutation in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess. Kitanaka, S., Katsumata, N., Tanae, A., Hibi, I., Takeyama, K., Fuse, H., Kato, S., Tanaka, T. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  32. Cloning and tissue distribution of the human 11 beta-hydroxysteroid dehydrogenase type 2 enzyme. Albiston, A.L., Obeyesekere, V.R., Smith, R.E., Krozowski, Z.S. Mol. Cell. Endocrinol. (1994) [Pubmed]
  33. Regulation of 11 beta-hydroxysteroid dehydrogenase type 2 activity and mRNA in human choriocarcinoma cells. Pasquarette, M.M., Stewart, P.M., Ricketts, M.L., Imaishi, K., Mason, J.I. J. Mol. Endocrinol. (1996) [Pubmed]
  34. Expression of 11 beta-hydroxysteroid dehydrogenase isozymes and corticosteroid hormone receptors in primary cultures of human trophoblast and placental bed biopsies. Driver, P.M., Kilby, M.D., Bujalska, I., Walker, E.A., Hewison, M., Stewart, P.M. Mol. Hum. Reprod. (2001) [Pubmed]
  35. The effect of growth hormone replacement therapy on cortisol-cortisone interconversion in hypopituitary adults: evidence for growth hormone modulation of extrarenal 11 beta-hydroxysteroid dehydrogenase activity. Gelding, S.V., Taylor, N.F., Wood, P.J., Noonan, K., Weaver, J.U., Wood, D.F., Monson, J.P. Clin. Endocrinol. (Oxf) (1998) [Pubmed]
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