HSD17B2

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External IDsGeneCards: [1]
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SpeciesHumanMouse
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17β-Hydroxysteroid dehydrogenase 2 (17β-HSD2) is an enzyme of the 17β-hydroxysteroid dehydrogenase (17β-HSD) family that in humans is encoded by the HSD17B2 gene.[1][2][3]

Function

17β-HSD2 is involved in inactivation of androgens and estrogens,[4] being accurately describable as "antiandrogenic" and "antiestrogenic",[5] and is the key 17β-HSD isozyme in androgen and estrogen inactivation.[4][additional citation(s) needed] Specific reactions catalyzed by 17β-HSD2 include estradiol to estrone, testosterone to androstenedione, and androstenediol to DHEA.[4][6] In addition to 17β-HSD activity, this enzyme also shows high 20α-hydroxysteroid dehydrogenase activity and can activate the weak progestogen 20α-hydroxyprogesterone into the potent progestogen progesterone.[4][6]

Expression

17β-HSD2 is widely expressed throughout the body including in the placenta, liver, intestines, endometrium, kidney, pancreas, breast, prostate, bone, and many other tissues.[7][8]

Clinical significance

Polymorphisms in HSD17B2 have been associated with breast cancer and prostate cancer.[9] 17β-HSD2 activity has also been associated with endometriosis and osteoporosis,[10] and inhibitors of the enzyme are of potential interest in the treatment of the latter condition.[11][12] Inactivating mutations resulting in a syndrome of congenital deficiency of 17β-HSD2 have not been reported to date.[13]

References

  1. ↑ Durocher F, Morissette J, Labrie Y, Labrie F, Simard J (Feb 1995). "Mapping of the HSD17B2 gene encoding type II 17 beta-hydroxysteroid dehydrogenase close to D16S422 on chromosome 16q24.1-q24.2". Genomics. 25 (3): 724–6. doi:10.1016/0888-7543(95)80017-G. PMID 7759109.
  2. ↑ Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jörnvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U (Mar 2009). "The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chemico-Biological Interactions. 178 (1–3): 94–8. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726.
  3. ↑ "Entrez Gene: HSD17B2 hydroxysteroid (17-beta) dehydrogenase 2".
  4. ↑ 4.0 4.1 4.2 4.3 Moeller G, Adamski J (2006). "Multifunctionality of human 17beta-hydroxysteroid dehydrogenases". Mol. Cell. Endocrinol. 248 (1–2): 47–55. doi:10.1016/j.mce.2005.11.031. PMID 16413960. 17β-HSD types 1–3, the key enzymes in homeostasis of steroid hormones (Andersson, 1995, Blomquist, 1995) seem to have their role solely in steroid metabolism catalysing reactions on steroid substrates only. [...] 17β-HSD2, an enzyme with broad tissue distribution (Casey et al., 1994), plays its major role in the inactivation of potent steroid hormones oxidising estradiol and testosterone to estrone and androstenedione, respectively (Wu et al., 1993). Beside this, 17β-oxidation of intermediates of steroid metabolism, e.g. 5α-androstane-3α,17β-diol, dihydrotestosterone and Δ5-androstene-3β,17β-diol is described (for review see Mindnich et al. (2004b). Additionally, human 17β-HSD type 2 has high 20α-HSD activity with progestins (Puranen et al., 1999).
  5. ↑ Wang CT, Li CF, Wu WJ, Huang CN, Li CC, Li WM, Chan TC, Liang PI, Hsing CH, Liao KM (2016). "High Expression of 17β-hydroxysteroid Dehydrogenase Type 2 is Associated with a Better Prognosis in Urothelial Carcinoma of the Urinary Tract". Journal of Cancer. 7 (15): 2221–2230. doi:10.7150/jca.16777. PMC 5166531. PMID 27994658. HSD17B2 has both anti-estrogenic and anti-androgenic functions.
  6. ↑ 6.0 6.1 Mindnich R, Möller G, Adamski J (2004). "The role of 17 beta-hydroxysteroid dehydrogenases". Mol. Cell. Endocrinol. 218 (1–2): 7–20. doi:10.1016/j.mce.2003.12.006. PMID 15130507.
  7. ↑ Hilborn E, Stål O, Jansson A (May 2017). "Estrogen and androgen-converting enzymes 17β-hydroxysteroid dehydrogenase and their involvement in cancer: with a special focus on 17β-hydroxysteroid dehydrogenase type 1, 2, and breast cancer". Oncotarget. 8 (18): 30552–30562. doi:10.18632/oncotarget.15547. PMC 5444764. PMID 28430630.
  8. ↑ Zhu Y, Imperato-McGinley JL (9 November 2016). "4.02: Disorders of Sexual Development in Males: Molecular Genetics, Epigenetics, Gender Identity, and Cognition". In Lightman S. Hormones, Brain and Behavior. 4: Clinical Important Effects of Hormones on Brain and Behavior. Elsevier Science. p. 69. ISBN 978-0-12-803608-2.
  9. ↑ Moeller G, Adamski J (2009). "Integrated view on 17beta-hydroxysteroid dehydrogenases". Mol. Cell. Endocrinol. 301 (1–2): 7–19. doi:10.1016/j.mce.2008.10.040. PMID 19027824.
  10. ↑ Bulun SE, Cheng YH, Pavone ME, Yin P, Imir G, Utsunomiya H, Thung S, Xue Q, Marsh EE, Tokunaga H, Ishikawa H, Kurita T, Su EJ (2010). "17Beta-hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis". Semin. Reprod. Med. 28 (1): 44–50. doi:10.1055/s-0029-1242992. PMC 4511594. PMID 20108182.
  11. ↑ Marchais-Oberwinkler S, Henn C, Möller G, Klein T, Negri M, Oster A, Spadaro A, Werth R, Wetzel M, Xu K, Frotscher M, Hartmann RW, Adamski J (2011). "17β-Hydroxysteroid dehydrogenases (17β-HSDs) as therapeutic targets: protein structures, functions, and recent progress in inhibitor development". J. Steroid Biochem. Mol. Biol. 125 (1–2): 66–82. doi:10.1016/j.jsbmb.2010.12.013. PMID 21193039.
  12. ↑ Soubhye J, Alard IC, van Antwerpen P, Dufrasne F (2015). "Type 2 17-β hydroxysteroid dehydrogenase as a novel target for the treatment of osteoporosis". Future Med Chem. 7 (11): 1431–56. doi:10.4155/fmc.15.74. PMID 26230882.
  13. ↑ J. Larry Jameson (13 July 1998). Principles of Molecular Medicine. Springer Science & Business Media. pp. 549–. ISBN 978-1-59259-726-0.

Further reading

  • Labrie Y, Durocher F, Lachance Y, Turgeon C, Simard J, Labrie C, Labrie F (Oct 1995). "The human type II 17 beta-hydroxysteroid dehydrogenase gene encodes two alternatively spliced mRNA species". DNA and Cell Biology. 14 (10): 849–61. doi:10.1089/dna.1995.14.849. PMID 7546291.
  • Andersson S, Geissler WM, Patel S, Wu L (Jun 1995). "The molecular biology of androgenic 17 beta-hydroxysteroid dehydrogenases". The Journal of Steroid Biochemistry and Molecular Biology. 53 (1–6): 37–9. doi:10.1016/0960-0760(95)00039-3. PMID 7626483.
  • Carsol JL, Martin PM, de Launoit Y (Oct 1994). "Characterization of 17 beta-hydroxysteroid dehydrogenase activity and mRNA abundance in human meningioma tumors". Neuroendocrinology. 60 (4): 445–51. doi:10.1159/000126779. PMID 7824086.
  • Wu L, Einstein M, Geissler WM, Chan HK, Elliston KO, Andersson S (Jun 1993). "Expression cloning and characterization of human 17 beta-hydroxysteroid dehydrogenase type 2, a microsomal enzyme possessing 20 alpha-hydroxysteroid dehydrogenase activity". The Journal of Biological Chemistry. 268 (17): 12964–9. PMID 8099587.
  • Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
  • Zhang Y, Word RA, Fesmire S, Carr BR, Rainey WE (Oct 1996). "Human ovarian expression of 17 beta-hydroxysteroid dehydrogenase types 1, 2, and 3". The Journal of Clinical Endocrinology and Metabolism. 81 (10): 3594–8. doi:10.1210/jc.81.10.3594. PMID 8855807.
  • Moghrabi N, Head JR, Andersson S (Nov 1997). "Cell type-specific expression of 17 beta-hydroxysteroid dehydrogenase type 2 in human placenta and fetal liver". The Journal of Clinical Endocrinology and Metabolism. 82 (11): 3872–8. doi:10.1210/jc.82.11.3872. PMID 9360554.
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
  • Corbould AM, Judd SJ, Rodgers RJ (Jan 1998). "Expression of types 1, 2, and 3 17 beta-hydroxysteroid dehydrogenase in subcutaneous abdominal and intra-abdominal adipose tissue of women". The Journal of Clinical Endocrinology and Metabolism. 83 (1): 187–94. doi:10.1210/jc.83.1.187. PMID 9435439.
  • Dong Y, Qiu QQ, Debear J, Lathrop WF, Bertolini DR, Tamburini PP (Oct 1998). "17Beta-hydroxysteroid dehydrogenases in human bone cells". Journal of Bone and Mineral Research. 13 (10): 1539–46. doi:10.1359/jbmr.1998.13.10.1539. PMID 9783542.
  • Kitawaki J, Koshiba H, Ishihara H, Kusuki I, Tsukamoto K, Honjo H (Sep 2000). "Progesterone induction of 17beta-hydroxysteroid dehydrogenase type 2 during the secretory phase occurs in the endometrium of estrogen-dependent benign diseases but not in normal endometrium". The Journal of Clinical Endocrinology and Metabolism. 85 (9): 3292–6. doi:10.1210/jc.85.9.3292. PMID 10999824.
  • Sano T, Hirasawa G, Takeyama J, Darnel AD, Suzuki T, Moriya T, Kato K, Sekine H, Ohara S, Shimosegawa T, Nakamura J, Yoshihama M, Harada N, Sasano H (Nov 2001). "17 beta-Hydroxysteroid dehydrogenase type 2 expression and enzyme activity in the human gastrointestinal tract". Clinical Science. 101 (5): 485–91. doi:10.1042/CS20010052. PMID 11672453.
  • Lu ML, Huang YW, Lin SX (Jun 2002). "Purification, reconstitution, and steady-state kinetics of the trans-membrane 17 beta-hydroxysteroid dehydrogenase 2". The Journal of Biological Chemistry. 277 (25): 22123–30. doi:10.1074/jbc.M111726200. PMID 11940569.
  • Provost PR, Blomquist CH, Drolet R, Flamand N, Tremblay Y (Aug 2002). "Androgen inactivation in human lung fibroblasts: variations in levels of 17 beta-hydroxysteroid dehydrogenase type 2 and 5 alpha-reductase activity compatible with androgen inactivation". The Journal of Clinical Endocrinology and Metabolism. 87 (8): 3883–92. doi:10.1210/jc.87.8.3883. PMID 12161528.
  • Oliveira IO, Lhullier C, Brum IS, Spritzer PM (Sep 2003). "Gene expression of type 2 17 beta hydroxysteroid dehydrogenase in scalp hairs of hirsute women". Steroids. 68 (7–8): 641–9. doi:10.1016/S0039-128X(03)00093-X. PMID 12957669.
  • Oduwole OO, Mäkinen JM, Isomaa VV, Karttunen TJ, Vihko PT (2004). "Sex steroid metabolism in human gastric mucosa: 17 beta-hydroxysteroid dehydrogenase type 2 in normal, inflamed and neoplastic gastric tissues". Anticancer Research. 23 (5A): 3889–97. PMID 14666693.
  • Matsuzaki S, Canis M, Pouly JL, Déchelotte PJ, Mage G (Feb 2006). "Analysis of aromatase and 17beta-hydroxysteroid dehydrogenase type 2 messenger ribonucleic acid expression in deep endometriosis and eutopic endometrium using laser capture microdissection". Fertility and Sterility. 85 (2): 308–13. doi:10.1016/j.fertnstert.2005.08.017. PMID 16595205.
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