Role of 5α-reductases in the prostate

5α-reductases convert testosterone to dihydrotestosterone(DHT).Two 5α-reductase isozymes,type 1 and type 2 are identified in humans and animals.Mutations in type 2 isozyme are responsible for male pseudohermaphroditism due to 5α-reductase deficiency.5α-reductase deficient 46XY subjects are born with ambiguous external genitalia with normal Wolffian differentiation.They have high normal or elevated plasma testosterone levels with low normal or decreased DHT levels,resulting in an elevated testosterone/DHT ratio. The prostate in these patients is small and rudimentary,and plasma levels of prostate specific antigen(PSA) are low or undetectable in adulthood.Prostate cancer and benign prostate hyperplasia(BPH) have never been reported.Animals with either 5α-reductase-2 or 5α-reductase-2 plus 5α-reductase-1 gene knockout,or treated with specific 5α-reductase inhibitor also have underdeveloped prostate.5α-reductase-2 is the predominant isozyme expressed in the human prostate.The expression of prostate 5α-reductase-2 gene is regulated by various factors such as dietary fat.A high dietary fat intake induces prostate 5αreductase-2 gene expression and subsequently stimulates prostate growth,which is blocked by genistein,a phytoestrogen.Inhibition of 5α-reductase activity by medication is used in the treatment of BPH and male-pattern baldness,while its use in prostate cancer prevention is still controversial although it can decrease the incidence of prostate cancer.The analyses of 5α-reductases in humans and animals highlight the differences between testosterone and DHT,and the significance of DHT in male sexual differentiation and prostate physiology and pathophysiology.