HSD17B2

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.[5][6][7]

HSD17B2
Identifiers
AliasesHSD17B2, EDH17B2, HSD17, SDR9C2, hydroxysteroid (17-beta) dehydrogenase 2, hydroxysteroid 17-beta dehydrogenase 2
External IDsOMIM: 109685 MGI: 1096386 HomoloGene: 99709 GeneCards: HSD17B2
EC number1.1.1.239
Orthologs
SpeciesHumanMouse
Entrez

3294

15486

Ensembl

ENSG00000086696

ENSMUSG00000031844

UniProt

P37059

P51658

RefSeq (mRNA)

NM_002153

NM_008290

RefSeq (protein)

NP_002144

NP_032316

Location (UCSC)Chr 16: 82.04 – 82.1 MbChr 8: 118.43 – 118.49 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

17β-HSD2 is involved in inactivation of androgens and estrogens,[8] being accurately describable as "antiandrogenic" and "antiestrogenic",[9] and is the key 17β-HSD isozyme in androgen and estrogen inactivation.[8] Specific reactions catalyzed by 17β-HSD2 include estradiol to estrone, testosterone to androstenedione, and androstenediol to DHEATooltip dehydroepiandrosterone.[8][10] 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.[8][10]

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.[11][12]

Clinical significance

Polymorphisms in HSD17B2 have been associated with breast cancer and prostate cancer.[13] 17β-HSD2 activity has also been associated with endometriosis and osteoporosis,[14] and inhibitors of the enzyme are of potential interest in the treatment of the latter condition.[15][16] Inactivating mutations resulting in a syndrome of congenital deficiency of 17β-HSD2 have not been reported to date.[17]

References
  1. GRCh38: Ensembl release 89: ENSG00000086696 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000031844 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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.
  6. 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.
  7. "Entrez Gene: HSD17B2 hydroxysteroid (17-beta) dehydrogenase 2".
  8. 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. S2CID 54235551. 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).
  9. 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.
  10. 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. S2CID 26877571.
  11. 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.
  12. 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 (ed.). Hormones, Brain and Behavior. Vol. 4: Clinical Important Effects of Hormones on Brain and Behavior. Elsevier Science. p. 69. ISBN 978-0-12-803608-2.
  13. 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. S2CID 30321495.
  14. 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.
  15. 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. S2CID 23767100.
  16. 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.
  17. J. Larry Jameson (13 July 1998). Principles of Molecular Medicine. Springer Science & Business Media. pp. 549–. ISBN 978-1-59259-726-0.

Further reading
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