Steroid 5-alpha-reductase type 1, Steroid 5-alpha-reductase type 2, Steroid 5-alpha-reductase type 3 (SRD5A1 (type 1), SRD5A2 (type 2), SRD5A3 (type 3))

Steroid 5-alpha-reductase type 1, type 2, and type 3 (SRD5A1, SRD5A2, and SRD5A3) are integral membrane NADPH-dependent oxidoreductase enzymes that catalyze the irreversible reduction of the Δ^4,5 double bond in 3-oxo-steroids to produce 5α-dihydrosteroids, most notably the conversion of testosterone to the potent androgen dihydrotestosterone (DHT)[1][3][5][7]. These isozymes are encoded by distinct genes (SRD5A1, SRD5A2, SRD5A3) and display differential tissue distribution and substrate selectivity. Type 2 is predominant in the prostate and essential for male sexual differentiation, while type 1 and 3 also contribute to androgen metabolism in other tissues. Mutations or dysregulation in these enzymes are implicated in a number of diseases, especially prostate disorders and androgen-dependent conditions. Clinically, SRD5A2 is the main therapeutic target for drugs such as finasteride and dutasteride, which are used in the treatment of benign prostatic hyperplasia, prostate cancer, and androgenetic alopecia[6][8]. Their mechanism involves competitive inhibition, reducing DHT levels and modifying androgen-dependent tissue growth. Safety concerns primarily involve effects from hormonal modulation.

Other names

3-oxo-5α-steroid 4-dehydrogenase5α-reductase 15α-reductase 25α-reductase 3

Competitive inhibition of 5α-reductase, blocking conversion of testosterone to dihydrotestosterone Specific binding (e.g., finasteride forms an adduct with NADPH and the enzyme) Indirect regulation via androgen receptor antagonism