AKR1C4

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.

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).

Isozymes

References

References

1. (February 2020). "Steroid enzyme and receptor expression and regulations in breast tumor samples - A statistical evaluation of public data". The Journal of Steroid Biochemistry and Molecular Biology.
2. (March 2008). "The complex roles of neurosteroids in depression and anxiety disorders". Neurochemistry International.
3. (December 2018). "The human genital tubercle is steroidogenic organ at early pregnancy". Molecular and Cellular Endocrinology.
4. (3 April 2023). ["Alternative androgen pathways"](https://upload.wikimedia.org/wikiversity/en/a/a7/Alternative_androgens_pathways.pdf}}{{Creative Commons text attribution notice). WikiJournal of Medicine.
5. (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.
6. {{EntrezGene. 1109 AKR1C4 aldo-keto reductase family 1 member C4 [ Homo sapiens (human) ]
7. (July 2003). "Human type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) and androgen metabolism in prostate cells". Endocrinology.
8. (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.
9. (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.
10. (March 2006). "Influence of mirtazapine on plasma concentrations of neuroactive steroids in major depression and on 3alpha-hydroxysteroid dehydrogenase activity". Molecular Psychiatry.