HSD3B1 explained

HSD3B1 is a human gene that encodes for a 3beta-hydroxysteroid dehydrogenase/delta(5)-delta(4)isomerase type I or hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1.^[1] While it can carry out the same function as HSD3B2, it localizes primarily to different tissues, such as the placenta and nonsteroidogenic tissues. Its requirement for the production of progesterone by the placenta, which has a vital role in pregnancy, may be one reason why no disease based on mutations in this gene has been identified to date, besides prostate cancer.

Clinical significance

The 1245C allele (HSD3B1 adrenal-permissive homozygous genotype 1245 C/C) encodes for a missense and hyperactive enzyme that increases extragonadal androgen synthesis and is associated with poorer outcomes after androgen deprivation therapy in prostate cancer.^{[2] [3] [4]}

References

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Further reading

• Dumont M, Luu-The V, Dupont E, Pelletier G, Labrie F . Characterization, expression, and immunohistochemical localization of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase in human skin . The Journal of Investigative Dermatology . 99 . 4 . 415–21 . October 1992 . 1401999 . 10.1111/1523-1747.ep12616131 .
• Russell AJ, Gaffney D, Gardiner MT, Nickson DA, Sutcliffe RG . Synonymous polymorphism in the coding sequence of human 3-beta hydroxysteroid-5-ene dehydrogenase (HSD) . Nucleic Acids Research . 19 . 5 . 1172 . March 1991 . 1673569 . 333834 . 10.1093/nar/19.5.1172-a .
• Lachance Y, Luu-The V, Labrie C, Simard J, Dumont M, de Launoit Y, Guérin S, Leblanc G, Labrie F . Characterization of human 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase gene and its expression in mammalian cells . The Journal of Biological Chemistry . 267 . 5 . 3551 . February 1992 . 10.1016/S0021-9258(19)50764-5 . 1737804 . free .
• Nickson DA, McBride MW, Zeinali S, Hawes CS, Petropoulos A, Mueller UW, Sutcliffe RG . Molecular cloning and expression of human trophoblast antigen FDO161G and its identification as 3 beta-hydroxy-5-ene steroid dehydrogenase . Journal of Reproduction and Fertility . 93 . 1 . 149–56 . September 1991 . 1920284 . 10.1530/jrf.0.0930149 . free .
• Rhéaume E, Lachance Y, Zhao HF, Breton N, Dumont M, de Launoit Y, Trudel C, Luu-The V, Simard J, Labrie F . Structure and expression of a new complementary DNA encoding the almost exclusive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase in human adrenals and gonads . Molecular Endocrinology . 5 . 8 . 1147–57 . August 1991 . 1944309 . 10.1210/mend-5-8-1147 . free .
• Morrison N, Nickson DA, McBride MW, Mueller UW, Boyd E, Sutcliffe RG . Regional chromosomal assignment of human 3-beta-hydroxy-5-ene steroid dehydrogenase to 1p13.1 by non-isotopic in situ hybridisation . Human Genetics . 87 . 2 . 223–5 . June 1991 . 2066113 . 10.1007/BF00204189 . 38702281 .
• Lorence MC, Corbin CJ, Kamimura N, Mahendroo MS, Mason JI . Structural analysis of the gene encoding human 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase . Molecular Endocrinology . 4 . 12 . 1850–5 . December 1990 . 2082186 . 10.1210/mend-4-12-1850 . free .
• Lorence MC, Murry BA, Trant JM, Mason JI . Human 3 beta-hydroxysteroid dehydrogenase/delta 5----4isomerase from placenta: expression in nonsteroidogenic cells of a protein that catalyzes the dehydrogenation/isomerization of C21 and C19 steroids . Endocrinology . 126 . 5 . 2493–8 . May 1990 . 2139411 . 10.1210/endo-126-5-2493 .
• Lachance Y, Luu-The V, Labrie C, Simard J, Dumont M, de Launoit Y, Guérin S, Leblanc G, Labrie F . Characterization of human 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase gene and its expression in mammalian cells . The Journal of Biological Chemistry . 265 . 33 . 20469–75 . November 1990 . 10.1016/S0021-9258(17)30528-8 . 2243100 . free .
• Luu The V, Lachance Y, Labrie C, Leblanc G, Thomas JL, Strickler RC, Labrie F . Full length cDNA structure and deduced amino acid sequence of human 3 beta-hydroxy-5-ene steroid dehydrogenase . Molecular Endocrinology . 3 . 8 . 1310–2 . August 1989 . 2779585 . 10.1210/mend-3-8-1310 . free .
• Thomas JL, Frieden C, Nash WE, Strickler RC . An NADH-induced conformational change that mediates the sequential 3 beta-hydroxysteroid dehydrogenase/isomerase activities is supported by affinity labeling and the time-dependent activation of isomerase . The Journal of Biological Chemistry . 270 . 36 . 21003–8 . September 1995 . 7673125 . 10.1074/jbc.270.36.21003 . free .
• Alvarez CI, Genti-Raimondi S, Patrito LC, Flury A . Topography of human placental 3 beta-hydroxysteroid dehydrogenase/delta 5-4 isomerase in microsomal membrane. A study using limited proteolysis and immunoblotting . Biochimica et Biophysica Acta . 1207 . 1 . 102–8 . July 1994 . 8043598 . 10.1016/0167-4838(94)90057-4 .
• Cherradi N, Defaye G, Chambaz EM . Dual subcellular localization of the 3 beta-hydroxysteroid dehydrogenase isomerase: characterization of the mitochondrial enzyme in the bovine adrenal cortex . The Journal of Steroid Biochemistry and Molecular Biology . 46 . 6 . 773–9 . December 1993 . 8274411 . 10.1016/0960-0760(93)90318-Q . 29330476 .
• Hatakeyama H, Miyamori I, Takeda Y, Yamamoto H, Mabuchi H . The expression of steroidogenic enzyme genes in human vascular cells . Biochemistry and Molecular Biology International . 40 . 3 . 639–45 . October 1996 . 8908375 . 10.1080/15216549600201233 . 26317546 .
• El-Alfy M, Luu-The V, Huang XF, Berger L, Labrie F, Pelletier G . Localization of type 5 17beta-hydroxysteroid dehydrogenase, 3beta-hydroxysteroid dehydrogenase, and androgen receptor in the human prostate by in situ hybridization and immunocytochemistry . Endocrinology . 140 . 3 . 1481–91 . March 1999 . 10067877 . 10.1210/endo.140.3.6585 . free .
• Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES . Characterization of single-nucleotide polymorphisms in coding regions of human genes . Nature Genetics . 22 . 3 . 231–8 . July 1999 . 10391209 . 10.1038/10290 . 195213008 .
• Bonenfant M, Provost PR, Drolet R, Tremblay Y . Localization of type 1 17beta-hydroxysteroid dehydrogenase mRNA and protein in syncytiotrophoblasts and invasive cytotrophoblasts in the human term villi . The Journal of Endocrinology . 165 . 2 . 217–22 . May 2000 . 10810285 . 10.1677/joe.0.1650217 . free .
• Pelletier G, Luu-The V, El-Alfy M, Li S, Labrie F . Immunoelectron microscopic localization of 3beta-hydroxysteroid dehydrogenase and type 5 17beta-hydroxysteroid dehydrogenase in the human prostate and mammary gland . Journal of Molecular Endocrinology . 26 . 1 . 11–9 . February 2001 . 11174850 . 10.1677/jme.0.0260011 . free .
• Pang S, Wang W, Rich B, David R, Chang YT, Carbunaru G, Myers SE, Howie AF, Smillie KJ, Mason JI . A novel nonstop mutation in the stop codon and a novel missense mutation in the type II 3beta-hydroxysteroid dehydrogenase (3beta-HSD) gene causing, respectively, nonclassic and classic 3beta-HSD deficiency congenital adrenal hyperplasia . The Journal of Clinical Endocrinology and Metabolism . 87 . 6 . 2556–63 . June 2002 . 10.1210/jcem.87.6.8559 . 12050213 . free .
• Rosmond R, Chagnon M, Bouchard C, Björntorp P . Polymorphism in exon 4 of the human 3 beta-hydroxysteroid dehydrogenase type I gene (HSD3B1) and blood pressure . Biochemical and Biophysical Research Communications . 293 . 1 . 629–32 . April 2002 . 12054649 . 10.1016/S0006-291X(02)00234-6 .

Notes and References

1. Web site: Entrez Gene: HSD3B1 Hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1.
2. Taneja SS . Re: HSD3B1 and Resistance to Androgen-Deprivation Therapy in Prostate Cancer: A Retrospective, Multicohort Study . The Journal of Urology . 197 . 1 . 150 . January 2017 . 27979506 . 10.1016/j.juro.2016.10.045 .
3. Hearn . Jason . HSD3B1 and resistance to androgen-deprivation therapy in prostate cancer: a retrospective, multicohort study . Lancet Oncology . October 2016 . 17 . 10 . 1435–1444 . 10.1016/S1470-2045(16)30227-3 . 27575027 . 5135009 .
4. McKay . Rana R. . Nelson . Tyler J. . Pagadala . Meghana S. . Teerlink . Craig C. . Gao . Anthony . Bryant . Alex K. . Agiri . Fatai Y. . Guram . Kripa . Thompson . Reid F. . Pridgen . Kathryn M. . Seibert . Tyler M. . Lee . Kyung Min . Carter . Hannah . Lynch . Julie A. . Hauger . Richard L. . 2024-03-20 . Adrenal-Permissive Germline HSD3B1 Allele and Prostate Cancer Outcomes . JAMA Network Open . 7 . 3 . e242976 . 10.1001/jamanetworkopen.2024.2976 . 2574-3805. 10955379 .
5. Chang . Kai-Hsiung . A gain-of-function mutation in DHT synthesis in castration-resistant prostate cancer . Cell . August 2013 . 154 . 5 . 1074–1084 . 10.1016/j.cell.2013.07.029 . 23993097 . 3931012 .