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 th at 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 strom al and epithelial cells from benign, hyperplastic adult prostates. MET HODS. [H-3]-thymidine incorporation was used as a measure of prolifera tion. Prostate-specific antigen (PSA) was quantified by ELISA and reve rse transcriptase-polymerase chain reaction (RT-PCR). RESULTS. Stromal cell proliferation in response to testosterone was dose-dependently i nhibited 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 and rogen-unresponsive stroma. Upregulation of PSA secretion from epitheli al cells by androgens was downregulated by epristeride (3 x 10(-9) M, P < 0.05) in testosterone-treated cells. Transforming growth factor be ta-1 (TGF beta-1) secretion was downregulated by testosterone treatmen t 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, In c.