The enzyme is produced in many tissues in both males and females, in the reproductive tract, testes and ovaries,[1] skin, seminal vesicles, prostate, epididymis and many organs,[2] including the nervous system.

5α-R1 and 5α-R2 are also expressed, although to different degrees in liver, genital and nongenital skin, prostate, epididymis, seminal vesicle, testis, ovary, uterus, kidney, exocrine pancreas, and the brain.

In vitro and animal models suggest subsequent 3alpha-reduction of DHT, DHP and DHDOC lead to steroid metabolites with effects on cerebral function achieved by enhancing GABAergic inhibition.

In socially isolated mice, 5α-R1 is specifically down-regulated in glutamatergic pyramidal neurons that converge on the amygdala from cortical and hippocampal regions.

Its formation in the kidney is enhanced by restriction of dietary salt, suggesting it may help retain sodium as follows:[12] 5α-DHP is a major hormone in circulation of normal cycling and pregnant women.

[14] 5α-Reductase is most known for converting testosterone, the male sex hormone, into the more potent dihydrotestosterone: The major difference is the Δ4,5 double-bond on the A (leftmost) ring.

The steroid-binding pocket contains a motif of Gln, Glu, and Tyr residues, which form a triad of hydrogen-bonds, which coordinate the C3 ketone of steroids into close proximity to the nicotinamide of NADPH, which allows a hydride transfer and Δ4 double-bond reduction.

[18] Additionally, it has been claimed that alfatradiol works through this mechanism of activity (5α-reductase), as well as the Ganoderic acids in lingzhi mushroom, and the Saw Palmetto.

[21] Finasteride decreases mean serum level of DHT by 71% after 6 months,[22] and was shown in vitro to inhibit 5α-R3 at a similar potency to 5α-R2 in transfected cell lines.

[2] Dutasteride inhibits 5α-reductase isoenzymes type 1 and 2 better than finasteride, leading to a more complete reduction in DHT at 24 weeks (94.7% versus 70.8%).

This is because 5α-reductase 2 catalyzes the transformation of testosterone to the potent androgen dihydrotestosterone, which is required for the proper masculinization of male genitalia.

[31] It has also shown the ability to reduce testosterone, androstenedione, and progesterone in androgen stimulated prostate cell lines by adenovirus vectors.

[8] Congenital deficiency of 5α-R3 at the gene SRD53A has been linked to a rare, autosomal recessive condition in which patients are born with severe intellectual dysfunction and cerebellar and ocular defects.

[32] Isolation rearing has been shown to lower protein expression of 5α-reductase isoenzymes 1 and 2 in cortical and subcortical brain regions of rat models.

Sleep deprivation can enhance 5α-reductase expression and activity in the prefrontal cortex, leading to mania-related symptoms in rats.

[39] Excess cortisol has been tied to metabolic dysfunction–associated steatotic liver disease (MASLD),  but in-vitro studies have found that an over expression of 5α-reductase type 2 can suppress lipogenesis.

In randomized studies on human volunteers it was found that 5α-reductase inhibition through the use of dutasteride and finasteride can lead to hepatic lipid accumulation in men.