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

Steroid 5α-reductase type 1 (SRD5A1) and type 2 (SRD5A2) are integral membrane oxidoreductase enzymes that catalyze the NADPH-dependent, irreversible reduction of the Δ4,5 double bond in 3-oxo-Δ^4^ steroids, most notably converting testosterone into the more potent androgen dihydrotestosterone (DHT)[3][4][5][6][8]. SRD5A2 is mainly expressed in the prostate and genital tissues and is critical for male sexual differentiation, while SRD5A1 is expressed in peripheral tissues (skin, liver, brain)[2][4][8]. Both are drug targets for conditions involving androgen excess, such as benign prostatic hyperplasia and prostate cancer, and are inhibited by drugs such as finasteride and dutasteride[5][6]. Mutations in SRD5A2 cause 5α-reductase deficiency, leading to disorders of sex development in individuals with a 46,XY karyotype[4]. Both enzymes share a conserved membrane topology with seven transmembrane domains and rely on NADPH as a hydride donor to convert substrates within the membrane[1][5][6][7].

Other names

3-oxo-5α-steroid 4-dehydrogenase 1 (SRD5A1)3-oxo-5α-steroid 4-dehydrogenase 2 (SRD5A2)5α-reductase type 15α-reductase type 2Steroid 5α-reductase 1 and 2EC 1.3.99.5

Competitive inhibition of steroid 5α-reductase to block conversion of testosterone to dihydrotestosterone (DHT); Irreversible enzyme inactivation (e.g., finasteride forms a stable adduct with the enzyme)