We evaluated the metabolic inhibitory, antiproliferative, and antisecretory effects of LY300502, a benzoquinolinone human-specific type I-selective steroid 5a-reductase inhibitor in LNCaP human prostatic adenocarcinoma cell cultures. Reductive metabolism of [3H-T] in the LNCaP cells was inhibited in
Effects of a new 5α reductase inhibitor (epristeride) on human prostate cell cultures
✍ Scribed by Robinson, Emma J.; Collins, Anne T.; Robson, Craig N.; Neal, David E.
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 150 KB
- Volume
- 32
- Category
- Article
- ISSN
- 0270-4137
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✦ Synopsis
BACKGROUND. Inhibitors of 5␣ reductase (5␣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␣R inhibitor, epristeride, on cultured stromal and epithelial cells from benign, hyperplastic adult prostates. METHODS. [ 3 H]-thymidine incorporation was used as a measure of proliferation. Prostatespecific 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 × 10 -9 -3 × 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 × 10 -9 M, P < 0.05) in testosterone-treated cells. Transforming growth factor -1 (TGF-1) secretion was downregulated by testosterone treatment and increased following treatment with epristeride (3 × 10 -9 M, P < 0.05). CONCLUSIONS. This demonstrates that epristeride specifically blocks testosterone-induced effects on prostatic cultures. TGF-1 may be a marker of 5␣ reductase activity.
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