5α‐Reductase Isozymes and Androgen Actions in the Prostate

Abstract

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 5alpha-reductase isozymes. Two 5alpha-reductase isozymes have been identified. Although both isozymes are expressed, 5alpha-reductase-2 is the predominant isozyme in the human prostate. Mutations in 5alpha-reductase-2 gene cause the 5alpha-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 5alpha-reductase-2 gene knockout or treated with specific 5alpha-reductase inhibitors. 5alpha-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 5alpha-reductases and androgen actions highlight the importance of 5alpha-reductase isozymes in male sexual differentiation and prostate physiology and pathophysiology.