HSD17B2

HSD17B2
Identifiers
Aliases	HSD17B2, EDH17B2, HSD17, SDR9C2, hydroxysteroid (17-beta) dehydrogenase 2, hydroxysteroid 17-beta dehydrogenase 2
External IDs	OMIM: 109685; MGI: 1096386; HomoloGene: 99709; GeneCards: HSD17B2; OMA:HSD17B2 - orthologs
EC number	1.1.1.239
Gene location (Human)
Chr.	Chromosome 16 (human)
End	82,098,534 bp
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)
End	118,485,766 bp
RNA expression pattern
	Top expressed in
	jejunal mucosa; ; duodenum; ; mucosa of transverse colon; ; mucosa of ileum; ; right lobe of liver; ; rectum; ; placenta; ; mucosa of urinary bladder; ; mucosa of sigmoid colon; ; olfactory zone of nasal mucosa;
	Top expressed in
	left lobe of liver; ; transitional epithelium of urinary bladder; ; left colon; ; esophagus; ; pyloric antrum; ; yolk sac; ; ileum; ; epithelium of stomach; ; jejunum; ; corneal stroma;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	oxidoreductase activity; testosterone dehydrogenase (NAD+) activity; 17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase activity; estradiol 17-beta-dehydrogenase activity;
Cellular component	integral component of membrane; endoplasmic reticulum membrane; membrane;
Biological process	in utero embryonic development; response to retinoic acid; steroid biosynthetic process; placenta development; lipid metabolism; estrogen biosynthetic process;
	Sources:Amigo / QuickGO
Orthologs
	3294
	15486
	ENSG00000086696
	ENSMUSG00000031844
	P37059
	P51658
	NM_002153
	NM_008290
	NP_002144
	NP_032316
	Wikidata
View/Edit Human	View/Edit Mouse

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.⁵⁶⁷

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.⁸¹⁰ 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.⁸¹⁰

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.¹¹¹²

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.¹⁵¹⁶ Inactivating mutations resulting in a syndrome of congenital deficiency of 17β-HSD2 have not been reported to date.¹⁷

References

GRCh38: Ensembl release 89: ENSG00000086696 – Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000031844 – Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Durocher F, Morissette J, Labrie Y, Labrie F, Simard J (February 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): 724–726. doi:10.1016/0888-7543(95)80017-G. PMID 7759109.
Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, et al. (March 2009). "The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chemico-Biological Interactions. 178 (1–3): 94–98. Bibcode:2009CBI...178...94P. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726.
"Entrez Gene: HSD17B2 hydroxysteroid (17-beta) dehydrogenase 2".
Moeller G, Adamski J (2006). "Multifunctionality of human 17beta-hydroxysteroid dehydrogenases". Molecular and Cellular Endocrinology. 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).
Wang CT, Li CF, Wu WJ, Huang CN, Li CC, Li WM, et al. (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.
Mindnich R, Möller G, Adamski J (2004). "The role of 17 beta-hydroxysteroid dehydrogenases". Molecular and Cellular Endocrinology. 218 (1–2): 7–20. doi:10.1016/j.mce.2003.12.006. PMID 15130507. S2CID 26877571.
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.
Zhu YS, 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.
Moeller G, Adamski J (2009). "Integrated view on 17beta-hydroxysteroid dehydrogenases". Molecular and Cellular Endocrinology. 301 (1–2): 7–19. doi:10.1016/j.mce.2008.10.040. PMID 19027824. S2CID 30321495.
Bulun SE, Cheng YH, Pavone ME, Yin P, Imir G, Utsunomiya H, et al. (2010). "17Beta-hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis". Seminars in Reproductive Medicine. 28 (1): 44–50. doi:10.1055/s-0029-1242992. PMC 4511594. PMID 20108182.
Marchais-Oberwinkler S, Henn C, Möller G, Klein T, Negri M, Oster A, et al. (2011). "17β-Hydroxysteroid dehydrogenases (17β-HSDs) as therapeutic targets: protein structures, functions, and recent progress in inhibitor development". The Journal of Steroid Biochemistry and Molecular Biology. 125 (1–2): 66–82. doi:10.1016/j.jsbmb.2010.12.013. PMID 21193039. S2CID 23767100.
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 Medicinal Chemistry. 7 (11): 1431–1456. doi:10.4155/fmc.15.74. PMID 26230882.
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, et al. (October 1995). "The human type II 17 beta-hydroxysteroid dehydrogenase gene encodes two alternatively spliced mRNA species". DNA and Cell Biology. 14 (10): 849–861. doi:10.1089/dna.1995.14.849. PMID 7546291.
Andersson S, Geissler WM, Patel S, Wu L (June 1995). "The molecular biology of androgenic 17 beta-hydroxysteroid dehydrogenases". The Journal of Steroid Biochemistry and Molecular Biology. 53 (1–6): 37–39. doi:10.1016/0960-0760(95)00039-3. PMID 7626483. S2CID 54417090.
Carsol JL, Martin PM, de Launoit Y (October 1994). "Characterization of 17 beta-hydroxysteroid dehydrogenase activity and mRNA abundance in human meningioma tumors". Neuroendocrinology. 60 (4): 445–451. doi:10.1159/000126779. PMID 7824086.
Wu L, Einstein M, Geissler WM, Chan HK, Elliston KO, Andersson S (June 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): 12964–12969. doi:10.1016/S0021-9258(18)31480-7. PMID 8099587.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Zhang Y, Word RA, Fesmire S, Carr BR, Rainey WE (October 1996). "Human ovarian expression of 17 beta-hydroxysteroid dehydrogenase types 1, 2, and 3". The Journal of Clinical Endocrinology and Metabolism. 81 (10): 3594–3598. doi:10.1210/jcem.81.10.8855807. PMID 8855807.
Moghrabi N, Head JR, Andersson S (November 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): 3872–3878. doi:10.1210/jcem.82.11.4391. PMID 9360554.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Corbould AM, Judd SJ, Rodgers RJ (January 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): 187–194. doi:10.1210/jcem.83.1.4495. PMID 9435439.
Dong Y, Qiu QQ, Debear J, Lathrop WF, Bertolini DR, Tamburini PP (October 1998). "17Beta-hydroxysteroid dehydrogenases in human bone cells". Journal of Bone and Mineral Research. 13 (10): 1539–1546. doi:10.1359/jbmr.1998.13.10.1539. PMID 9783542. S2CID 85168465.
Kitawaki J, Koshiba H, Ishihara H, Kusuki I, Tsukamoto K, Honjo H (September 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): 3292–3296. doi:10.1210/jcem.85.9.6829. PMID 10999824. S2CID 23016515.
Sano T, Hirasawa G, Takeyama J, Darnel AD, Suzuki T, Moriya T, et al. (November 2001). "17 beta-Hydroxysteroid dehydrogenase type 2 expression and enzyme activity in the human gastrointestinal tract". Clinical Science. 101 (5). London: 485–491. doi:10.1042/CS20010052. PMID 11672453.
Lu ML, Huang YW, Lin SX (June 2002). "Purification, reconstitution, and steady-state kinetics of the trans-membrane 17 beta-hydroxysteroid dehydrogenase 2". The Journal of Biological Chemistry. 277 (25): 22123–22130. doi:10.1074/jbc.M111726200. PMID 11940569.
Provost PR, Blomquist CH, Drolet R, Flamand N, Tremblay Y (August 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): 3883–3892. doi:10.1210/jcem.87.8.8764. PMID 12161528.
Oliveira IO, Lhullier C, Brum IS, Spritzer PM (September 2003). "Gene expression of type 2 17 beta hydroxysteroid dehydrogenase in scalp hairs of hirsute women". Steroids. 68 (7–8): 641–649. doi:10.1016/S0039-128X(03)00093-X. PMID 12957669. S2CID 22194313.
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): 3889–3897. PMID 14666693.
Matsuzaki S, Canis M, Pouly JL, Déchelotte PJ, Mage G (February 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): 308–313. doi:10.1016/j.fertnstert.2005.08.017. PMID 16595205.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000086696 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[Durocher_1995-5] Durocher F, Morissette J, Labrie Y, Labrie F, Simard J (February 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): 724–726. doi:10.1016/0888-7543(95)80017-G. PMID 7759109.

[Persson_2009-6] Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, et al. (March 2009). "The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chemico-Biological Interactions. 178 (1–3): 94–98. Bibcode:2009CBI...178...94P. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726.

[entrez-7] "Entrez Gene: HSD17B2 hydroxysteroid (17-beta) dehydrogenase 2".

[Moeller_2006-8] Moeller G, Adamski J (2006). "Multifunctionality of human 17beta-hydroxysteroid dehydrogenases". Molecular and Cellular Endocrinology. 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).

[Wang_2016-9] Wang CT, Li CF, Wu WJ, Huang CN, Li CC, Li WM, et al. (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.

[Mindnich_2004-10] Mindnich R, Möller G, Adamski J (2004). "The role of 17 beta-hydroxysteroid dehydrogenases". Molecular and Cellular Endocrinology. 218 (1–2): 7–20. doi:10.1016/j.mce.2003.12.006. PMID 15130507. S2CID 26877571.

[Hilborn_2017-11] 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.

[Elsevier2016-12] Zhu YS, 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.

[Moeller_2009-13] Moeller G, Adamski J (2009). "Integrated view on 17beta-hydroxysteroid dehydrogenases". Molecular and Cellular Endocrinology. 301 (1–2): 7–19. doi:10.1016/j.mce.2008.10.040. PMID 19027824. S2CID 30321495.

[Bulun_2010-14] Bulun SE, Cheng YH, Pavone ME, Yin P, Imir G, Utsunomiya H, et al. (2010). "17Beta-hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis". Seminars in Reproductive Medicine. 28 (1): 44–50. doi:10.1055/s-0029-1242992. PMC 4511594. PMID 20108182.

[Marchais-Oberwinkler_2011-15] Marchais-Oberwinkler S, Henn C, Möller G, Klein T, Negri M, Oster A, et al. (2011). "17β-Hydroxysteroid dehydrogenases (17β-HSDs) as therapeutic targets: protein structures, functions, and recent progress in inhibitor development". The Journal of Steroid Biochemistry and Molecular Biology. 125 (1–2): 66–82. doi:10.1016/j.jsbmb.2010.12.013. PMID 21193039. S2CID 23767100.

[Soubhye_2015-16] 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 Medicinal Chemistry. 7 (11): 1431–1456. doi:10.4155/fmc.15.74. PMID 26230882.

[Jameson1998-17] J. Larry Jameson (13 July 1998). Principles of Molecular Medicine. Springer Science & Business Media. pp. 549–. ISBN 978-1-59259-726-0.

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