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
[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 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.
Robinson
E J
EJ
Department of Surgery, Medical School, University of Newcastle, Newcastle upon Tyne, United Kingdom.
Collins
A T
AT
Robson
C N
CN
Neal
D E
DE
D058891:5-alpha Reductase Inhibitors; D000328:Adult; D000730:Androstadienes / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000032:analysis / Q000096:biosynthesis; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D012333:RNA, Messenger / Q000096:biosynthesis; D013739:Testosterone / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis
D058891:5-alpha Reductase Inhibitors; D000730:Androstadienes; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D013196:Dihydrotestosterone; C072547:epristeride; D013739:Testosterone; D017430:Prostate-Specific Antigen; D013936:Thymidine