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5α-Reductase Isozymes and Androgen Actions in the Prostate


Address for correspondence: Yuan-Shan Zhu, M.D., Ph.D., Department of Medicine/Endocrinology, Weill Cornell Medical College, 1300 York Avenue, Box 149, New York, New York 10065. Voice: 212-746-8348; fax: 212-746-7698.


Androgens acting via the androgen receptor play critical roles in prostate development, growth, and pathogenesis. There are two potent androgens, testosterone and dihydrotestosterone (DHT), in humans and mammals. DHT is converted from testosterone by 5α-reductase isozymes. Two 5α-reductase isozymes have been identified. Although both isozymes are expressed, 5α-reductase-2 is the predominant isozyme in the human prostate. Mutations in 5α-reductase-2 gene cause the 5α-reductase-2 deficiency syndrome. Affected 46, XY individuals have a small, nonpalpable, and rudimentary prostate in adulthood. Neither benign prostate hyperplasia (BPH) nor prostate cancer has been reported in these patients. The prostate is small in animals with 5α-reductase-2 gene knockout or treated with specific 5α-reductase inhibitors. 5α-reductase isozymes are molecular targets for the prevention and treatment of BPH and prostate cancer. Moreover, androgen actions on prostate gene expression and cell growth are directly modulated by estrogen receptor ligands via protein−protein interactions. The studies of 5α-reductases and androgen actions highlight the importance of 5α-reductase isozymes in male sexual differentiation and prostate physiology and pathophysiology.