AKR1C4

{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox_gene}} '''Aldo-keto reductase family 1 member C4''', also known as '''3α-Hydroxysteroid dehydrogenase type 1''' ('''3α-HSD1'''),<ref>{{cite journal | vauthors = Li T, Zhang W, Lin SX | title = Steroid enzyme and receptor expression and regulations in breast tumor samples - A statistical evaluation of public data | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 196 | article-number = 105494 | date = February 2020 | pmid = 31610224 | doi = 10.1016/j.jsbmb.2019.105494 }}</ref><ref>{{cite journal | vauthors = Longone P, Rupprecht R, Manieri GA, Bernardi G, Romeo E, Pasini A | title = The complex roles of neurosteroids in depression and anxiety disorders | journal = Neurochemistry International | volume = 52 | issue = 4–5 | pages = 596–601 | date = March 2008 | pmid = 17996986 | doi = 10.1016/j.neuint.2007.10.001 }}</ref><ref>{{cite journal | vauthors = Savchuk I, Morvan ML, Antignac JP, Gemzell-Danielsson K, Le Bizec B, Söder O, Svechnikov K | title = The human genital tubercle is steroidogenic organ at early pregnancy | journal = Molecular and Cellular Endocrinology | volume = 477 | pages = 148–155 | date = December 2018 | pmid = 29928928 | doi = 10.1016/j.mce.2018.06.012 }}</ref> is an enzyme that in humans is encoded by the ''AKR1C4'' gene.<ref name="wj">{{cite journal |doi=10.15347/WJM/2023.003 |doi-access=free |title=Alternative androgen pathways |date=3 April 2023 | vauthors = Masiutin MM, Yadav MK |journal=WikiJournal of Medicine |volume=10 |pages=29 |s2cid=257943362 |url=https://upload.wikimedia.org/wikiversity/en/a/a7/Alternative_androgens_pathways.pdf}}{{Creative Commons text attribution notice|cc=by4|from this source=yes}}</ref><ref name="pmid7789999">{{cite journal | vauthors = Khanna M, Qin KN, Klisak I, Belkin S, Sparkes RS, Cheng KC | title = Localization of multiple human dihydrodiol dehydrogenase (DDH1 and DDH2) and chlordecone reductase (CHDR) genes in chromosome 10 by the polymerase chain reaction and fluorescence in situ hybridization | journal = Genomics | volume = 25 | issue = 2 | pages = 588–590 | date = January 1995 | pmid = 7789999 | doi = 10.1016/0888-7543(95)80066-U | doi-access = free }}</ref><ref name="entrez">{{EntrezGene|1109}} AKR1C4 aldo-keto reductase family 1 member C4 [ Homo sapiens (human) ]</ref> It is known to be necessary for the synthesis of the endogenous neurosteroids allopregnanolone, tetrahydrodeoxycorticosterone, and 3α-androstanediol. It is also known to catalyze the reversible conversion of 3α-androstanediol (5α-androstane-3α,17β-diol) to dihydrotestosterone (DHT, 5α-androstan-17β-ol-3-one) and vice versa.<ref name="pmid12810547">{{cite journal | vauthors = Rizner TL, Lin HK, Peehl DM, Steckelbroeck S, Bauman DR, Penning TM | title = Human type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) and androgen metabolism in prostate cells | journal = Endocrinology | volume = 144 | issue = 7 | pages = 2922–2932 | date = July 2003 | pmid = 12810547 | doi = 10.1210/en.2002-0032 | doi-access = free }}</ref>

== Function == This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the bioreduction of chlordecone, a toxic organochlorine pesticide, to chlordecone alcohol in liver. This gene shares high sequence identity with three other gene members and is clustered with those three genes at 10p15-p14 on chromosome 10.<ref name="entrez"/>

== Clinical significance == Various antidepressants, including the SSRIs fluoxetine, fluvoxamine, sertraline, and paroxetine, the SNRI venlafaxine, and mirtazapine, have been found to activate certain isoforms of the 3α-hydroxysteroid dehydrogenase, resulting in a selective facilitation of 5α-dihydroprogesterone conversion into allopregnanolone. This action has been implicated in their effectiveness in affective disorders, and has resulted in them being described as ''selective brain steroidogenic stimulants'' (SBSSs).<ref name="pmid10557352">{{cite journal | vauthors = Griffin LD, Mellon SH | title = Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 23 | pages = 13512–13517 | date = November 1999 | pmid = 10557352 | pmc = 23979 | doi = 10.1073/pnas.96.23.13512 | doi-access = free | bibcode = 1999PNAS...9613512G }}</ref><ref name="pmid20716970">{{cite journal | vauthors = Pinna G | title = In a mouse model relevant for post-traumatic stress disorder, selective brain steroidogenic stimulants (SBSS) improve behavioral deficits by normalizing allopregnanolone biosynthesis | journal = Behavioural Pharmacology | volume = 21 | issue = 5–6 | pages = 438–450 | date = September 2010 | pmid = 20716970 | pmc = 2942072 | doi = 10.1097/FBP.0b013e32833d8ba0 }}</ref><ref name="pmid16344854">{{cite journal | vauthors = Schüle C, Romeo E, Uzunov DP, Eser D, di Michele F, Baghai TC, Pasini A, Schwarz M, Kempter H, Rupprecht R | title = Influence of mirtazapine on plasma concentrations of neuroactive steroids in major depression and on 3alpha-hydroxysteroid dehydrogenase activity | journal = Molecular Psychiatry | volume = 11 | issue = 3 | pages = 261–272 | date = March 2006 | pmid = 16344854 | doi = 10.1038/sj.mp.4001782 | s2cid = 21473462 | doi-access = }}</ref>

== Isozymes == {{AKR1CN}}

== References == {{Reflist}} {{Clear}}

== Further reading == {{refbegin|30em}} * {{cite journal | vauthors = Binstock JM, Iyer RB, Hamby CV, Fried VA, Schwartz IS, Weinstein BI, Southren AL | title = Human hepatic 3 alpha-hydroxysteroid dehydrogenase: possible identity with human hepatic chlordecone reductase | journal = Biochemical and Biophysical Research Communications | volume = 187 | issue = 2 | pages = 760–766 | date = September 1992 | pmid = 1530633 | doi = 10.1016/0006-291X(92)91260-W | bibcode = 1992BBRC..187..760B }} * {{cite journal | vauthors = Winters CJ, Molowa DT, Guzelian PS | title = Isolation and characterization of cloned cDNAs encoding human liver chlordecone reductase | journal = Biochemistry | volume = 29 | issue = 4 | pages = 1080–1087 | date = January 1990 | pmid = 2187532 | doi = 10.1021/bi00456a034 }} * {{cite journal | vauthors = Khanna M, Qin KN, Cheng KC | title = Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and molecular cloning of multiple cDNAs encoding structurally related proteins in humans | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 53 | issue = 1–6 | pages = 41–46 | date = June 1995 | pmid = 7626489 | doi = 10.1016/0960-0760(95)00019-V | s2cid = 11316547 | doi-access = free }} * {{cite journal | vauthors = Khanna M, Qin KN, Wang RW, Cheng KC | title = Substrate specificity, gene structure, and tissue-specific distribution of multiple human 3 alpha-hydroxysteroid dehydrogenases | journal = The Journal of Biological Chemistry | volume = 270 | issue = 34 | pages = 20162–20168 | date = August 1995 | pmid = 7650035 | doi = 10.1074/jbc.270.34.20162 | doi-access = free }} * {{cite journal | vauthors = Deyashiki Y, Ogasawara A, Nakayama T, Nakanishi M, Miyabe Y, Sato K, Hara A | title = Molecular cloning of two human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzymes that are identical with chlordecone reductase and bile-acid binder | journal = The Biochemical Journal | volume = 299 ( Pt 2) | issue = Pt 2 | pages = 545–552 | date = April 1994 | pmid = 8172617 | pmc = 1138306 | doi = 10.1042/bj2990545 }} * {{cite journal | vauthors = Qin KN, New MI, Cheng KC | title = Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3 alpha-hydroxysteroid dehydrogenase | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 46 | issue = 6 | pages = 673–679 | date = December 1993 | pmid = 8274401 | doi = 10.1016/0960-0760(93)90308-J | s2cid = 36210133 }} * {{cite journal | vauthors = Kume T, Iwasa H, Shiraishi H, Yokoi T, Nagashima K, Otsuka M, Terada T, Takagi T, Hara A, Kamataki T | title = Characterization of a novel variant (S145C/L311V) of 3alpha-hydroxysteroid/dihydrodiol dehydrogenase in human liver | journal = Pharmacogenetics | volume = 9 | issue = 6 | pages = 763–771 | date = December 1999 | pmid = 10634139 | doi = 10.1097/00008571-199912000-00011 }} * {{cite journal | vauthors = Nishizawa M, Nakajima T, Yasuda K, Kanzaki H, Sasaguri Y, Watanabe K, Ito S | title = Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes | journal = Genes to Cells | volume = 5 | issue = 2 | pages = 111–125 | date = February 2000 | pmid = 10672042 | doi = 10.1046/j.1365-2443.2000.00310.x | s2cid = 25136637 | doi-access = free }} * {{cite journal | vauthors = Dufort I, Labrie F, Luu-The V | title = Human types 1 and 3 3 alpha-hydroxysteroid dehydrogenases: differential lability and tissue distribution | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 86 | issue = 2 | pages = 841–846 | date = February 2001 | pmid = 11158055 | doi = 10.1210/jcem.86.2.7216 | doi-access = free }} * {{cite journal | vauthors = Ozeki T, Takahashi Y, Kume T, Nakayama K, Yokoi T, Nunoya K, Hara A, Kamataki T | title = Co-operative regulation of the transcription of human dihydrodiol dehydrogenase (DD)4/aldo-keto reductase (AKR)1C4 gene by hepatocyte nuclear factor (HNF)-4alpha/gamma and HNF-1alpha | journal = The Biochemical Journal | volume = 355 | issue = Pt 2 | pages = 537–544 | date = April 2001 | pmid = 11284743 | pmc = 1221767 | doi = 10.1042/0264-6021:3550537 }} * {{cite journal | vauthors = Ozeki T, Takahashi Y, Nakayama K, Kamataki T | title = Hepatocyte nuclear factor (HNF)-4 alpha/gamma, HNF-1 alpha, and vHNF-1 regulate the cell-specific expression of the human dihydrodiol dehydrogenase (DD)4/AKR1C4 gene | journal = Archives of Biochemistry and Biophysics | volume = 405 | issue = 2 | pages = 185–190 | date = September 2002 | pmid = 12220531 | doi = 10.1016/S0003-9861(02)00384-3 }} * {{cite journal | vauthors = Ozeki T, Takahashi Y, Nakayama K, Funayama M, Nagashima K, Kodama T, Kamataki T | title = Hepatocyte nuclear factor-4 alpha/gamma and hepatocyte nuclear factor-1 alpha as causal factors of interindividual difference in the expression of human dihydrodiol dehydrogenase 4 mRNA in human livers | journal = Pharmacogenetics | volume = 13 | issue = 1 | pages = 49–53 | date = January 2003 | pmid = 12544512 | doi = 10.1097/00008571-200301000-00007 }} * {{cite journal | vauthors = Schüle C, Romeo E, Uzunov DP, Eser D, di Michele F, Baghai TC, Pasini A, Schwarz M, Kempter H, Rupprecht R | title = Influence of mirtazapine on plasma concentrations of neuroactive steroids in major depression and on 3alpha-hydroxysteroid dehydrogenase activity | journal = Molecular Psychiatry | volume = 11 | issue = 3 | pages = 261–272 | date = March 2006 | pmid = 16344854 | doi = 10.1038/sj.mp.4001782 | s2cid = 21473462 | doi-access = }} {{refend}}

== External links == * {{UCSC gene info|AKR1C4}}

Category:EC 1.1.1

AKR1C4

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