Aldo-keto reductase family 1 member C4, also known as 3ñ-Hydroxysteroid dehydrogenase type 1 (3ñ-HSD1), is an enzyme that in humans is encoded by the AKR1C4 gene. It is known to be necessary for the synthesis of the endogenous neurosteroids allopregnanolone, tetrahydrodeoxycorticosterone, and 3ñ-androstanediol. It is also known to catalyze the reversible conversion of 3ñ-androstanediol (5ñ-androstane-3ñ,17ò-diol) to dihydrotestosterone (DHT, 5ñ-androstan-17ò-ol-3-one) and vice versa.
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.
Various antidepressants, including the SSRIs fluoxetine, fluvoxamine, sertraline, and paroxetine, the SNRI venlafaxine, and mirtazapine, have been found to activate certain isoforms of the 3ñ-hydroxysteroid dehydrogenase, resulting in a selective facilitation of 5ñ-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).