3α-Hydroxysteroid dehydrogenase

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AKR1C4
Protein AKR1C4 PDB 2fvl.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases AKR1C4, 3-alpha-HSD, C11, CDR, CHDR, DD-4, DD4, HAKRA, aldo-keto reductase family 1, member C4, aldo-keto reductase family 1 member C4
External IDs MGI: 1933427 HomoloGene: 84695 GeneCards: AKR1C4
EC number 1.1.1.225
RNA expression pattern
PBB GE AKR1C4 210558 at fs.png

PBB GE AKR1C1 211653 x at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001818

NM_030611

RefSeq (protein)

NP_001809

NP_085114

Location (UCSC) Chr 10: 5.2 – 5.22 Mb Chr 13: 4.43 – 4.46 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

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.[3][4] 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.[5]

Function[edit]

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.[4]

Clinical significance[edit]

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).[6][7][8]

See also[edit]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ 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. PMID 7789999. doi:10.1016/0888-7543(95)80066-U. 
  4. ^ a b "Entrez Gene: AKR1C4 aldo-keto reductase family 1, member C4 (chlordecone reductase; 3-alpha hydroxysteroid dehydrogenase, type I; dihydrodiol dehydrogenase 4)". 
  5. ^ 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. PMID 12810547. doi:10.1210/en.2002-0032. 
  6. ^ 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. PMC 23979Freely accessible. PMID 10557352. doi:10.1073/pnas.96.23.13512. 
  7. ^ 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. PMC 2942072Freely accessible. PMID 20716970. doi:10.1097/FBP.0b013e32833d8ba0. 
  8. ^ 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. PMID 16344854. doi:10.1038/sj.mp.4001782. 

External links[edit]

Further reading[edit]