| 释义 |
- Function
- Clinical significance
- See also
- References
- External links
- Further reading
{{Infobox_gene}}3α-Hydroxysteroid dehydrogenase (3α-HSD or aldo-keto reductase family 1 member C4) is an enzyme that in humans is encoded by the AKR1C4 gene.[1][2] It is known to be necessary for the synthesis of the endogenous neurosteroids allopregnanolone, THDOC, 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.[3] 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.[2] Clinical significance Various antidepressants, including the SSRIs fluoxetine, fluvoxamine, sertraline, and paroxetine, the SNRI venlafaxine, and mirtazapine, have been found to activate certain 3α-HSD enzymes, 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).[4][5][6] See also- Steroidogenic enzyme
- 3α-hydroxysteroid dehydrogenase type 3
- 3β-Hydroxysteroid dehydrogenase
References 1. ^{{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 = 588–90 | date = January 1995 | pmid = 7789999 | pmc = | doi = 10.1016/0888-7543(95)80066-U }}
2. ^1 {{cite web | title = Entrez Gene: AKR1C4 aldo-keto reductase family 1, member C4 (chlordecone reductase; 3-alpha hydroxysteroid dehydrogenase, type I; dihydrodiol dehydrogenase 4)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1109| accessdate = }}
3. ^{{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 = 2922–32 | date = July 2003 | pmid = 12810547 | doi = 10.1210/en.2002-0032 }}
4. ^{{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 = 13512–7 | date = November 1999 | pmid = 10557352 | pmc = 23979 | doi = 10.1073/pnas.96.23.13512 }}
5. ^{{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 = 438–50 | date = September 2010 | pmid = 20716970 | pmc = 2942072 | doi = 10.1097/FBP.0b013e32833d8ba0 }}
6. ^{{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 = 261–72 | date = March 2006 | pmid = 16344854 | doi = 10.1038/sj.mp.4001782 }}
{{Clear}}External links- {{UCSC gene info|AKR1C4}}
Further reading {{refbegin|35em}}- {{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 = 760–6 | date = September 1992 | pmid = 1530633 | doi = 10.1016/0006-291X(92)91260-W }}
- {{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 = 1080–7 | 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 = 41–6 | date = June 1995 | pmid = 7626489 | doi = 10.1016/0960-0760(95)00019-V }}
- {{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 = 20162–8 | date = August 1995 | pmid = 7650035 | doi = 10.1074/jbc.270.34.20162 }}
- {{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 = 2 | pages = 545–52 | 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 = 673–9 | date = December 1993 | pmid = 8274401 | doi = 10.1016/0960-0760(93)90308-J }}
- {{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 = 763–71 | 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 = 111–25 | date = February 2000 | pmid = 10672042 | doi = 10.1046/j.1365-2443.2000.00310.x }}
- {{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 = 841–6 | date = February 2001 | pmid = 11158055 | doi = 10.1210/jc.86.2.841 }}
- {{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 = 537–44 | 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 = 185–90 | 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 = 261–72 | date = March 2006 | pmid = 16344854 | doi = 10.1038/sj.mp.4001782 }}
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