3α-Hydroxysteroid dehydrogenase: Difference between revisions

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{{Infobox_gene}}
{{Infobox_gene}}
'''3α-hydroxysteroid dehydrogenase''' ('''3α-HSD'''), also known as '''aldo-keto reductase family 1 member C4''', is an [[enzyme]] that in humans is encoded by the ''AKR1C4'' [[gene]].<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 = 588–90 | date = January 1995 | pmid = 7789999 | pmc =  | doi = 10.1016/0888-7543(95)80066-U }}</ref><ref name="entrez">{{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 = }}</ref> It is known to be necessary for the [[biosynthesis|synthesis]] of the [[endogenous]] [[neurosteroid]]s [[allopregnanolone]], [[tetrahydrodeoxycorticosterone|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.<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 = 2922–32 | date = July 2003 | pmid = 12810547 | doi = 10.1210/en.2002-0032 }}</ref>
'''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]].<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 = 588–90 | date = January 1995 | pmid = 7789999 | pmc =  | doi = 10.1016/0888-7543(95)80066-U }}</ref><ref name="entrez">{{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 = }}</ref> It is known to be necessary for the [[biosynthesis|synthesis]] of the [[endogenous]] [[neurosteroid]]s [[allopregnanolone]], [[tetrahydrodeoxycorticosterone|THDOC]], and [[3α-Androstanediol|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 = 2922–32 | date = July 2003 | pmid = 12810547 | doi = 10.1210/en.2002-0032 }}</ref>


== Function ==
== Function ==
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== Clinical significance ==
== Clinical significance ==


Various [[antidepressant]]s, including the [[selective serotonin reuptake inhibitor|SSRI]]s [[fluoxetine]], [[fluvoxamine]], [[sertraline]], and [[paroxetine]], the [[serotonin-norepinephrine reuptake inhibitor|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 stimulant]]s'' (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 = 13512–7 | date = November 1999 | pmid = 10557352 | pmc = 23979 | doi = 10.1073/pnas.96.23.13512 }}</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 = 438–50 | 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 = 261–72 | date = March 2006 | pmid = 16344854 | doi = 10.1038/sj.mp.4001782 }}</ref>
Various [[antidepressant]]s, including the [[selective serotonin reuptake inhibitor|SSRI]]s [[fluoxetine]], [[fluvoxamine]], [[sertraline]], and [[paroxetine]], the [[serotonin-norepinephrine reuptake inhibitor|SNRI]] [[venlafaxine]], and [[mirtazapine]], have been found to activate certain 3α-HSD enzymes, resulting in a selective facilitation of [[5α-Dihydroprogesterone|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 stimulant]]s'' (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 = 13512–7 | date = November 1999 | pmid = 10557352 | pmc = 23979 | doi = 10.1073/pnas.96.23.13512 }}</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 = 438–50 | 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 = 261–72 | date = March 2006 | pmid = 16344854 | doi = 10.1038/sj.mp.4001782 }}</ref>


==See also==
==See also==
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[[Category:EC 1.1.1]]
[[Category:EC 1.1.1]]
{{gene-10-stub}}

Latest revision as of 23:30, 11 November 2018

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Orthologs
SpeciesHumanMouse
Entrez
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RefSeq (protein)

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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

References

  1. Khanna M, Qin KN, Klisak I, Belkin S, Sparkes RS, Cheng KC (January 1995). "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". Genomics. 25 (2): 588–90. doi:10.1016/0888-7543(95)80066-U. PMID 7789999.
  2. 2.0 2.1 "Entrez Gene: AKR1C4 aldo-keto reductase family 1, member C4 (chlordecone reductase; 3-alpha hydroxysteroid dehydrogenase, type I; dihydrodiol dehydrogenase 4)".
  3. Rizner TL, Lin HK, Peehl DM, Steckelbroeck S, Bauman DR, Penning TM (July 2003). "Human type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) and androgen metabolism in prostate cells". Endocrinology. 144 (7): 2922–32. doi:10.1210/en.2002-0032. PMID 12810547.
  4. Griffin LD, Mellon SH (November 1999). "Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes". Proceedings of the National Academy of Sciences of the United States of America. 96 (23): 13512–7. doi:10.1073/pnas.96.23.13512. PMC 23979. PMID 10557352.
  5. Pinna G (September 2010). "In a mouse model relevant for post-traumatic stress disorder, selective brain steroidogenic stimulants (SBSS) improve behavioral deficits by normalizing allopregnanolone biosynthesis". Behavioural Pharmacology. 21 (5–6): 438–50. doi:10.1097/FBP.0b013e32833d8ba0. PMC 2942072. PMID 20716970.
  6. Schüle C, Romeo E, Uzunov DP, Eser D, di Michele F, Baghai TC, Pasini A, Schwarz M, Kempter H, Rupprecht R (March 2006). "Influence of mirtazapine on plasma concentrations of neuroactive steroids in major depression and on 3alpha-hydroxysteroid dehydrogenase activity". Molecular Psychiatry. 11 (3): 261–72. doi:10.1038/sj.mp.4001782. PMID 16344854.

External links

Further reading