Effects of a new 5α reductase inhibitor (Epristeride) on human prostate cell cultures

Inhibitors of 5α reductase (5αR), 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 5αR inhibitor, epristeride, on cultured stromal and epithelial cells from benign, hyperplastic adult prostates. METHODS. [³H]-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 β-1 (TGFβ-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. TGFβ-1 may be a marker of 5α reductase activity.