Steroid 5α-reductase 1 and Steroid 5α-reductase 2 (SRD5A1 and SRD5A2)

Steroid 5α-reductase 1 and 2 are integral membrane oxidoreductase enzymes that catalyze the NADPH-dependent reduction of testosterone to dihydrotestosterone (DHT), a more potent androgen essential for male sexual differentiation, prostate development, and androgen-responsive tissue physiology. Both enzymes share a conserved seven-transmembrane-domain (7-TM) architecture and use NADPH as a cofactor. SRD5A2 is primarily expressed in the prostate and is important for developing and maintaining male external genitalia and prostate growth, while SRD5A1 has a broader tissue distribution and is implicated in skin and hair follicle androgen metabolism. Mutations in SRD5A2 cause 5α-reductase deficiency, a disorder of sexual development in 46,XY individuals. Pharmacological inhibition of these enzymes—by drugs such as finasteride (SRD5A2 selective) and dutasteride (dual SRD5A1/2 inhibitor)—is clinically important in the treatment of benign prostatic hyperplasia, androgenetic alopecia, and potentially prostate cancer.

Other names

5α-reductase type 15α-reductase type 23-oxo-5α-steroid 4-dehydrogenase 1 (for type 1)3-oxo-5α-steroid 4-dehydrogenase 2 (for type 2)SRD5A1, SRD5A25AR1, 5AR2

Competitive inhibition of enzyme to block conversion of testosterone to dihydrotestosterone (DHT); Dual inhibition of both isozymes (dutasteride); selective inhibition of type 2 (finasteride)