5α-Reductase Isozymes in the Prostate.
5α-reductases convert testosterone to dihydrotestosterone (DHT). There are two 5α-reductase isozymes, type 1 and type 2 in humans and animals. Mutations in type 2 isozyme with decreased enzymatic activity cause male pseudohermaphroditism. The affected 46XY individuals have high normal or elevated plasma testosterone levels with low normal or decreased DHT levels, resulting in an elevated testosterone/DHT ratios. They are born with ambiguous external genitalia and normal Wolffian differentiation. Their prostate 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 in these patients. Similar defects in prostate development are observed in animals with either 5α-reductase-2 or 5α-reductase-2 plus 5α-reductase-1 gene knockout, and in animals treated with specific 5α-reductase inhibitor. 5α-reductase isozymes are expressed in multiple tissues, and the predominant isozyme in human prostate is 5α-reductase-2. The expression of 5α-reductase-2 gene in prostate cells is regulated by various factors. A high dietary fat intake, a risk factor of prostate cancer, induces prostate 5α-reductase-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.
Zhu
Yuan-Shan
YS
Sun
Guang-Huan
GH