17Beta Hydroxysteroid dehydrogenase

17β-Hydroxysteroid dehydrogenase
EC no.
CAS no.9015-81-0
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

17β-Hydroxysteroid dehydrogenases (17β-HSD, HSD17B) (EC, also 17-ketosteroid reductases (17-KSR), are a group of alcohol oxidoreductases which catalyze the reduction of 17-ketosteroids and the dehydrogenation of 17β-hydroxysteroids in steroidogenesis and steroid metabolism.[1][2][3][4][5] This includes interconversion of DHEA and androstenediol, androstenedione and testosterone, and estrone and estradiol.[6][7]

The major reactions catalyzed by 17β-HSD (e.g., the conversion of androstenedione to testosterone) are in fact hydrogenation (reduction) rather than dehydrogenation (oxidation) reactions.


Steroidogenesis. 17β-HSD visible in bottom-left region.

17β-HSDs have been known to catalyze the following redox reactions of sex steroids:

Activity distribution[]

Distribution of 17β-HSD activities for formation of estradiol versus estrone in human tissues.[8][9]


Genes coding for 17β-HSD include:

At least 7 of the 14 isoforms of 17β-HSD are involved in interconversion of 17-ketosteroids and 17β-hydroxysteroids.[12]


Comparison and characteristics of human 17β-HSD isoenzymes[27][28][29][30]
# Gene name Synonyms Family Size (AA) Gene location Cellular location Substrate specificities Preferred cofactor Catalytic preference Tissue distribution Expression profile Pathology
1 HSD17B1 SDR 328 17q21.2 Cytosol Estrogens NADH, NADPH Reduction Ovary, endometrium, breast, brain, prostate, placenta Strongly restricted Breast cancer, prostate cancer, endometriosis
2 HSD17B2 SDR 387 16q23.3 ER Estrogens, androgens, progestogens NAD+ Oxidation Liver, intestine, endometrium, placenta, pancreas, prostate, colon, bone Selectively distributed Breast cancer, prostate cancer, endometriosis, osteoporosis[31]
3 HSD17B3 SDR 310 9q22.32 ER Androgens NADPH Reduction Testis, ovary, blood, saliva, skin, adipose tissue, brain, bone Strongly restricted 17β-HSD3 deficiency, prostate cancer[32]
4 HSD17B4 DBP, MFP2 SDR 736 5q23.1 PXS Fatty acids, bile acids, estrogens, androgens NAD+ Oxidation Liver, heart, prostate, testis, lung, skeletal muscle, kidney, pancreas, thymus, ovary, intestine, placenta, brain, spleen, colon, lymphocytes Ubiquitous DBP deficiency, Perrault syndrome, prostate cancer
5 AKR1C3 HSD17B5, PGFS AKR 323 10p15.1 Nucleus, cytosol Androgens, progestogens, estrogens, prostaglandins NADPH Reduction Prostate, mammary gland, liver, kidney, lung, heart, small intestine, colon, uterus, testis, brain, skeletal muscle, adipose tissue Nearly ubiquitous Breast cancer, prostate cancer
6 HSD17B6 SDR 317 12q13.3 Endosomes Retinoids, androgens, estrogens NAD+ Oxidation Liver, testis, lung, spleen, brain, ovary, kidney, adrenal, prostate Selectively distributed ?
7 HSD17B7 SDR 341 1q23.3 PM, ER Cholesterol, estrogens, androgens, progestogens NADPH Reduction Ovary, corpus luteum, uterus, placenta, liver, breast, testis, brain, adrenal gland, small intestine, lung, thymus, prostate, adipose tissue, others Widely distributed Breast cancer
8 HSD17B8 SDR 261 6p21.32 MC Fatty acids, estrogens, androgens NAD+ Oxidation Prostate, placenta, kidney, brain, cerebellum, heart, lung, small intestine, ovary, testis, adrenal, stomach Widely distributed Polycystic kidney disease
9 RDH5 HSD17B9 318 12q13.2 ER Retinoids NADH/NAD+ Reduction / oxidation Retina, liver, adipose tissue, blood, others ? Fundus albipunctatus
10 HSD17B10 MHBD SDR 261 Xp11.2 MC Fatty acids, bile acids, estrogens, androgens, progestogens, corticosteroids NAD+ Oxidation Liver, small intestine, colon, kidney, heart, brain, placenta, lung, ovary, testis, spleen, thymus, prostate, peripheral blood leukocytes Nearly ubiquitous 17β-HSD10 deficiency, MRXS10, Alzheimer's disease
11 HSD17B11 SDR 300 4q22.1 ER, EP Estrogens, androgens NAD+ Oxidation Liver, pancreas, intestine, kidney, adrenal gland, heart, lung, testis, ovary, placenta, sebaceous gland Nearly ubiquitous ?
12 HSD17B12 SDR 312 11p11.2 ER Fatty acids, estrogens, androgens NADPH Reduction Heart, skeletal muscle, liver, kidney, adrenal gland, testis, placenta, cerebellum, pancreas, stomach, small intestine, large intestine, trachea, lung, thyroid, esophagus, prostate, aorta, urinary bladder, spleen, skin, brain, ovary, breast, uterus, vagina Ubiquitous ?
13 HSD17B13 SDR 300 4q22.1 ER, EP ? NAD+? Oxidation? Liver, bone marrow, lung, ovary, testis, kidney, skeletal muscle, brain, bladder, nasal epithelia Strongly restricted ?
14 HSD17B14 SDR 270 19q13.33 Cytosol Estrogens, androgens, fatty acids NAD+ Oxidation Liver, kidney, brain, gallbladder, breast, adrenal, placenta Widely distributed Breast cancer (prognostic)
15 RDH11[33][34][35] PSDR1, HSD17B15 SDR 318 14q23-24.3 ER Retinoids, androgens NADPH Reduction Retina, prostate, brain, testis ? Retinitis pigmentosa[36]

Clinical significance[]

Mutations in HSD17B3 are responsible for 17β-HSD type III deficiency.

Inhibitors of 17β-HSD type II are of interest for the potential treatment of osteoporosis.[31][37]

Some inhibitors of 17β-HSD type I have been identified, for example esters of cinnamic acid and various flavones (e.g. fisetin).[38]

See also[]


  1. ^ Dahm K, Breuer H (1964). "Anreicherung einer 17β-hydroxysteroid:NAD(P)-oxydoreduktase aus der Nebenniere der Ratte" [Precipitation of a 17-Beta-Hydroxysteroid:Nad(P) Oxidoreductase from the Rat Adrenal Gland]. Hoppe-Seyler's Zeitschrift für Physiologische Chemie (in German). 336: 63–8. doi:10.1515/bchm2.1964.336.1.63. PMID 14214322.
  2. ^ Lynn WS, Brown RH (June 1958). "The conversion of progesterone to androgens by testes". The Journal of Biological Chemistry. 232 (2): 1015–30. doi:10.1016/S0021-9258(19)77419-5. PMID 13549484.
  3. ^ Marcus PI, Talalay P (February 1956). "Induction and purification of alpha- and beta-hydroxysteroid dehydrogenases". The Journal of Biological Chemistry. 218 (2): 661–74. doi:10.1016/S0021-9258(18)65833-8. PMID 13295221.
  4. ^ Schultz RM, Groman EV, Engel LL (June 1977). "3(17)beta-Hydroxysteroid dehydrogenase of Pseudomonas testosteroni. A convenient purification and demonstration of multiple molecular forms". The Journal of Biological Chemistry. 252 (11): 3775–83. doi:10.1016/S0021-9258(17)40319-X. PMID 193845.
  5. ^ Talalay P, Dobson MM (December 1953). "Purification and properties of a beta-hydroxysteroid dehydrogenase". The Journal of Biological Chemistry. 205 (2): 823–37. doi:10.1016/S0021-9258(18)49226-5. PMID 13129261.
  6. ^ Labrie F, Luu-The V, Lin SX, Labrie C, Simard J, Breton R, Bélanger A (January 1997). "The key role of 17 beta-hydroxysteroid dehydrogenases in sex steroid biology". Steroids. 62 (1): 148–58. doi:10.1016/S0039-128X(96)00174-2. PMID 9029730. S2CID 54365519.
  7. ^ Brook CG, Truong D, Clayton P, Carroll W, Brown R (2011). Brook's Clinical Pediatric Endocrinology. John Wiley & Sons. p. 288. ISBN 978-1-4443-1673-5.
  8. ^ Martel C, Rhéaume E, Takahashi M, Trudel C, Couët J, Luu-The V, Simard J, Labrie F (March 1992). "Distribution of 17 beta-hydroxysteroid dehydrogenase gene expression and activity in rat and human tissues". J. Steroid Biochem. Mol. Biol. 41 (3–8): 597–603. doi:10.1016/0960-0760(92)90390-5. PMID 1314080. S2CID 54325300.
  9. ^ Michael Oettel; Ekkehard Schillinger (6 December 2012). Estrogens and Antiestrogens I: Physiology and Mechanisms of Action of Estrogens and Antiestrogens. Springer Science & Business Media. p. 226. ISBN 978-3-642-58616-3.
  10. ^ a b c d 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.
  11. ^ Aka JA, Mazumdar M, Chen CQ, Poirier D, Lin SX (April 2010). "17beta-hydroxysteroid dehydrogenase type 1 stimulates breast cancer by dihydrotestosterone inactivation in addition to estradiol production". Molecular Endocrinology. 24 (4): 832–45. doi:10.1210/me.2009-0468. PMC 5417535. PMID 20172961.
  12. ^ a b c d e f g h Strauss JF, Barbieri RL (13 September 2013). Yen and Jaffe's Reproductive Endocrinology. Elsevier Health Sciences. p. 82. ISBN 978-1-4557-2758-2.
  13. ^ Andersson S, Moghrabi N (January 1997). "Physiology and molecular genetics of 17 beta-hydroxysteroid dehydrogenases". Steroids. 62 (1): 143–7. doi:10.1016/s0039-128x(96)00173-0. PMID 9029729. S2CID 54341481.
  14. ^ a b Jameson JL (13 July 1998). Principles of Molecular Medicine. Springer Science & Business Media. p. 549. ISBN 978-1-59259-726-0.
  15. ^ Hakkarainen J, Jokela H, Pakarinen P, Heikelä H, Kätkänaho L, Vandenput L, Ohlsson C, Zhang FP, Poutanen M (September 2015). "Hydroxysteroid (17β)-dehydrogenase 1-deficient female mice present with normal puberty onset but are severely subfertile due to a defect in luteinization and progesterone production". FASEB Journal. 29 (9): 3806–16. doi:10.1096/fj.14-269035. PMID 26018678.
  16. ^ 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.
  17. ^ a b Melmed S (2016). Williams Textbook of Endocrinology. Elsevier Health Sciences. p. 904. ISBN 978-0-323-29738-7.
  18. ^ Jameson JL, De Groot LJ (25 February 2015). Endocrinology: Adult and Pediatric E-Book. Elsevier Health Sciences. p. 2078. ISBN 978-0-323-32195-2.
  19. ^ 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 (January 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.
  20. ^ a b Pierce SB, Walsh T, Chisholm KM, Lee MK, Thornton AM, Fiumara A, Opitz JM, Levy-Lahad E, Klevit RE, King MC (August 2010). "Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome". American Journal of Human Genetics. 87 (2): 282–8. doi:10.1016/j.ajhg.2010.07.007. PMC 2917704. PMID 20673864.
  21. ^ Fomitcheva J, Baker ME, Anderson E, Lee GY, Aziz N (August 1998). "Characterization of Ke 6, a new 17beta-hydroxysteroid dehydrogenase, and its expression in gonadal tissues". The Journal of Biological Chemistry. 273 (35): 22664–71. doi:10.1074/jbc.273.35.22664. PMID 9712896.
  22. ^ Kikuti YY, Tamiya G, Ando A, Chen L, Kimura M, Ferreira E, Tsuji K, Trowsdale J, Inoko H (June 1997). "Physical mapping 220 kb centromeric of the human MHC and DNA sequence analysis of the 43-kb segment including the RING1, HKE6, and HKE4 genes". Genomics. 42 (3): 422–35. doi:10.1006/geno.1997.4745. PMID 9205114.
  23. ^ Lidén M, Tryggvason K, Eriksson U (December 2003). "Structure and function of retinol dehydrogenases of the short chain dehydrogenase/reductase family". Molecular Aspects of Medicine. 24 (6): 403–9. doi:10.1016/s0098-2997(03)00036-0. PMID 14585311.
  24. ^ Skorczyk-Werner A, Pawłowski P, Michalczuk M, Warowicka A, Wawrocka A, Wicher K, Bakunowicz-Łazarczyk A, Krawczyński MR (August 2015). "Fundus albipunctatus: review of the literature and report of a novel RDH5 gene mutation affecting the invariant tyrosine (p.Tyr175Phe)". Journal of Applied Genetics. 56 (3): 317–27. doi:10.1007/s13353-015-0281-x. PMC 4543405. PMID 25820994.
  25. ^ a b Yang SY, He XY, Miller D (2011). "Hydroxysteroid (17β) dehydrogenase X in human health and disease". Mol. Cell. Endocrinol. 343 (1–2): 1–6. doi:10.1016/j.mce.2011.06.011. PMID 21708223. S2CID 8608312.
  26. ^ a b Yang SY, He XY, Isaacs C, Dobkin C, Miller D, Philipp M (2014). "Roles of 17β-hydroxysteroid dehydrogenase type 10 in neurodegenerative disorders". J. Steroid Biochem. Mol. Biol. 143: 460–72. doi:10.1016/j.jsbmb.2014.07.001. PMID 25007702.
  27. ^ 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. 4: Clinical Important Effects of Hormones on Brain and Behavior. Elsevier Science. p. 69. ISBN 978-0-12-803608-2.
  28. ^ 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.
  29. ^ 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.
  30. ^ 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.
  31. ^ a b 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.
  32. ^ Ning X, Yang Y, Deng H, Zhang Q, Huang Y, Su Z, Fu Y, Xiang Q, Zhang S (2017). "Development of 17β-hydroxysteroid dehydrogenase type 3 as a target in hormone-dependent prostate cancer therapy". Steroids. 121: 10–16. doi:10.1016/j.steroids.2017.02.003. PMID 28267564. S2CID 32062736.
  33. ^ Samson M, Labrie F, and Luu-The V (23 June 2012). "Characterization of Type 15 17β-Hydroxysteroid Dehydrogenase". Steroid Hormone Biosynthesis & Metabolism (Translational). doi:10.1210/endo-meetings.2012.
  34. ^ Lin B, White JT, Ferguson C, Wang S, Vessella R, Bumgarner R, True LD, Hood L, Nelson PS (2001). "Prostate short-chain dehydrogenase reductase 1 (PSDR1): a new member of the short-chain steroid dehydrogenase/reductase family highly expressed in normal and neoplastic prostate epithelium". Cancer Res. 61 (4): 1611–8. PMID 11245473.
  35. ^ Kedishvili NY, Chumakova OV, Chetyrkin SV, Belyaeva OV, Lapshina EA, Lin DW, Matsumura M, Nelson PS (2002). "Evidence that the human gene for prostate short-chain dehydrogenase/reductase (PSDR1) encodes a novel retinal reductase (RalR1)". J. Biol. Chem. 277 (32): 28909–15. doi:10.1074/jbc.M202588200. PMID 12036956.
  36. ^ Xie YA, Lee W, Cai C, Gambin T, Nõupuu K, Sujirakul T, Ayuso C, Jhangiani S, Muzny D, Boerwinkle E, Gibbs R, Greenstein VC, Lupski JR, Tsang SH, Allikmets R (2014). "New syndrome with retinitis pigmentosa is caused by nonsense mutations in retinol dehydrogenase RDH11". Hum. Mol. Genet. 23 (21): 5774–80. doi:10.1093/hmg/ddu291. PMC 4189905. PMID 24916380.
  37. ^ Perspicace E, Cozzoli L, Gargano EM, Hanke N, Carotti A, Hartmann RW, Marchais-Oberwinkler S (August 2014). "Novel, potent and selective 17β-hydroxysteroid dehydrogenase type 2 inhibitors as potential therapeutics for osteoporosis with dual human and mouse activities". European Journal of Medicinal Chemistry. 83: 317–37. doi:10.1016/j.ejmech.2014.06.036. PMID 24974351.
  38. ^ Brozic P, Kocbek P, Sova M, Kristl J, Martens S, Adamski J, Gobec S, Lanisnik Rizner T (March 2009). "Flavonoids and cinnamic acid derivatives as inhibitors of 17beta-hydroxysteroid dehydrogenase type 1". Molecular and Cellular Endocrinology. 301 (1–2): 229–34. doi:10.1016/j.mce.2008.09.004. PMID 18835421. S2CID 26950431.

External links[]