The mechanism of epristeride against benign prostatic hyperplasia.
Epristeride, a 5alpha-reductase inhibitor, decreases prostate size and improves symptoms in men with benign prostatic hyperplasia. However, little is known about the histopathology of the prostate after treatment with epristeride. To study the relationship between apoptosis and the mechanism of epristeride in the treatment of benign prostatic hyperplasia, the induction of apoptosis by epristeride was detected and measured in vitro by: (a) observing morphological changes in cells by light microscopy; (b) comparing the relative content of dihydrotestosterone in the rat prostate epithelial cells untreated and treated with epristeride by microspectrophotometry; (c) estimating changes in cell size and DNA integrity by flow cytometry; and (d) monitoring nucleosomal DNA fragmentation by agarose gel electrophoresis. The cells treated with epristeride showed a reduction in cell size, an increase in the cytoplasm/nuclear ratio, which is indicative of the condensation of nuclear chromatin, a significant decrease in optical density at 580 nm (OD580 nm), and an oligonucleosomal ladder and a subdiploid peak of DNA characteristic of apoptosis. Therefore, the mechanism of epristeride in the treatment of benign prostatic hyperplasia might be apoptosis stimulated by decreasing dihydrotestosterone level.
Sun
Z Y
ZY
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences. sunzuyue@server.shcnc.ac.cn
Wu
H Y
HY
Wang
M Y
MY
Tu
Z H
ZH
D000730:Androstadienes / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques; D048429:Cell Size / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D013196:Dihydrotestosterone / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008297:Male; D008853:Microscopy; D015591:Microspectrophotometry; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000730:Androstadienes; D004791:Enzyme Inhibitors; D013196:Dihydrotestosterone; C072547:epristeride