Effects of a new 5 alpha reductase inhibitor (epristeride) on human prostate cell cultures

BACKGROUND. Inhibitors of 5 alpha reductase (5 alpha R), the enzyme that converts testosterone to dihydrotestosterone (DHT), have been shown to retard the growth of hyperplastic prostates. This study evaluates the effects of the 5 alpha R inhibitor, epristeride, on cultured stromal and epithelial cells from benign, hyperplastic adult prostates. METHODS. [H-3]-thymidine incorporation was used as a measure of proliferation. Prostate-specific antigen (PSA) was quantified by ELISA and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS. Stromal cell proliferation in response to testosterone was dose-dependently inhibited by epristeride (1 x 10(-9) - 3 x 10(-7) M, P < 0.05). However, epristeride had no effect on DHT-induced growth or the growth of androgen-unresponsive stroma. Upregulation of PSA secretion from epithelial cells by androgens was downregulated by epristeride (3 x 10(-9) M, P < 0.05) in testosterone-treated cells. Transforming growth factor beta-1 (TGF beta-1) secretion was downregulated by testosterone treatment and increased following treatment with epristeride (3 x 10(-9) M, P < 0.05). CONCLUSIONS. This demonstrates that epristeride specifically blocks testosterone-induced effects on prostatic cultures. TGF beta-1 may be a marker of 5 alpha reductase activity. (C) 1997 Wiley-Liss, Inc.