Reproductive toxicological study on epristeride

Benign protate hyperplasia (BPH) is a common disease in older men.Epristeride is an uncompetitive inhibitor of steroid 5α-reductase,the enzyme that converts testosterone to dihydrotestosterone (DHT),and has been shown to retard the growth of hyperplastic prostates.The study included the toxicological effects of epristeride on prostate,vas deferens and sperm.The results were listed below.(1)The 180 days toxicity of epristeride (100mg·kg^-1) on interstitial cells of Beagle dog tests and DNA in prostatic epithelial cells couldn't reverse during 60 days vonvalescence,and that the DHT and prostate specific antigen (PSA) level in the gland,the volume of the grland,glandular epithelial cell height and acinar luminal area could reverse to normal during the same convalescence.(2)It was demonstrated that an apoptosis of vas deferens epithelial cell of SD rat was observed at the concentration of 0.3 and 1.0nmol·L^-1 epristeride in vitro.The results of PCR showed the exkpression of bcl-2 on vas deferens epithelial cells treated or untreated with epristeride,but the sequence of bcl-2 did not altered.(3)Motility and motile rate of sperm of rat,dog and human in vitro were videotaped and analyzed with computer-assisted sperm anaysis(CASA) system after 1h and 2h incubation.MOT(the percentage of motile sperm) of Beagle dog sperm were significantly reduced after treated with 0.6,6 and 60μmol·L^-1 epristeride,respectively,but no significant change occurred in SD rat and human at the same concertations of epristeride.Is a word,epristeride is a better drug against BPH though there are much reproductive toxicity.