3-alpha-HSD

3α-hydroxysteroid dehydrogenase (3α-HSD), also known as aldo-keto reductase family 1 member C4, is an is_associated_with::enzyme that in humans is encoded by the AKR1C4 is_associated_with::gene. It is known to be necessary for the synthesis of the is_associated_with::endogenous is_associated_with::neurosteroids is_associated_with::allopregnanolone, THDOC, and is_associated_with::3α-androstanediol. It is also known to catalyze the reversible conversion of 3α-androstanediol (5α-androstane-3α,17β-diol) to is_associated_with::dihydrotestosterone (DHT) (5α-androstan-17β-ol-3-one) and vice versa.

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 is_associated_with::NADH and/or is_associated_with::NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the bioreduction of is_associated_with::chlordecone, a toxic organochlorine pesticide, to chlordecone alcohol in is_associated_with::liver. This gene shares high sequence identity with three other gene members and is clustered with those three genes at is_associated_with::chromosome 10p15-p14.

Clinical significance
Various is_associated_with::antidepressants, including the SSRIs is_associated_with::fluoxetine, is_associated_with::fluvoxamine, is_associated_with::sertraline, and is_associated_with::paroxetine, the SNRI is_associated_with::venlafaxine, and is_associated_with::mirtazapine, have been found to activate certain 3α-HSD enzymes, resulting in a selective facilitation of is_associated_with::5α-dihydroprogesterone conversion into allopregnanolone. This action has been implicated in their effectiveness in affective disorders, and has resulted in them being described as is_associated_with::selective brain steroidogenic stimulants (SBSSs).