5α-Reductase Isozymes and Androgen Actions in the Prostate

Androgens, particularly testosterone and dihydrotestosterone (DHT), played crucial roles in prostate development and pathology, with DHT being converted from testosterone by 5α‐reductase isozymes. Two isozymes were identified, with 5α‐reductase‐2 being predominant in the human prostate. Mutations in the 5α‐reductase‐2 gene caused a deficiency syndrome, leading to a small, rudimentary prostate in affected individuals, who did not develop benign prostate hyperplasia (BPH) or prostate cancer. Animal studies with 5α‐reductase‐2 gene knockout or specific inhibitors also showed reduced prostate size. These isozymes were key targets for preventing and treating BPH and prostate cancer, and androgen actions on prostate gene expression and growth were modulated by estrogen receptor ligands. The research underscored the significance of 5α‐reductase isozymes in male sexual differentiation and prostate health.