Steroid 5 alpha-reductase type 1 (SRD5A1) and Steroid 5 alpha-reductase type 2 (SRD5A2) (SRD5A1; SRD5A2)

Steroid 5 alpha-reductase type 1 and type 2 are membrane-bound enzymes that irreversibly reduce the Δ^4,5 double bond in steroid substrates, most notably converting testosterone to dihydrotestosterone (DHT), the key ligand for androgen receptor activation in prostate and other androgen-sensitive tissues. They use NADPH as a cofactor and are encoded by distinct genes (SRD5A1 on chromosome 5 and SRD5A2 on chromosome 2). Differential expression of these enzymes is implicated in prostate cancer progression, with type 2 prevalent in normal prostate and type 1 upregulated in cancer. Inhibition of these enzymes forms the basis of medical management for benign prostatic hyperplasia and some androgen-dependent cancers, while loss-of-function mutations in SRD5A2 can cause developmental disorders in genetic males.

Other names

3-Oxo-5α-steroid 4-dehydrogenase 15α-reductase type 13-Oxo-5α-steroid 4-dehydrogenase 25α-reductase type 2

Inhibition of enzymatic conversion of testosterone to DHT, reducing androgenic activity in target tissues; Blockade or downregulation of androgen receptor-mediated transcriptional regulation of SRD5A1 and SRD5A2