Effect of epristeride on the expression of IGF-1 and TGF-beta receptors in androgen-induced castrated rat prostate.
The development of benign prostatic hyperplasia (BPH) is an androgen-dependent process that may be mediated by a number of locally produced growth factors. Among them, insulin-like growth factor 1 (IGF-1) and transforming growth factor beta (TGF beta) are thought important in regulating prostate growth and homeostasis, and their expression undergoes changes in proliferative prostatic disease. Epristeride, a 5 alpha-reductase inhibitor, is an effective drug in the treatment of BPH, inducing regressive changes in the prostate. This study was designed to assess the effects of epristeride on expression of these two factors at mRNA and protein levels in castrated rats maintained with exogenous testosterone. Epristeride treatment caused significant reduction in ventral prostate weight in a dose-dependent manner. There was a positive correlation between IGF-1 mRNA expression and ventral prostate weight and an inverse correlation between TGF-beta 1 mRNA expression and ventral prostate weight. Immunohistochemistry showed strong IGF-1 receptor immunoreactivity in the prostatic epithelial cells of untreated animals. In situ hybridization demonstrated high levels of IGF-1 mRNA expression both in the prostatic stromal and epithelial cells of untreated rats. In treated rats, both IGF-1 receptor protein and IGF-1 mRNA levels decreased significantly, and IGF-1 mRNA was mainly expressed in prostatic stromal cells. Weak expression of TGF beta receptors at the protein level and TGF beta at the mRNA level were found in the prostatic hyperplastic epithelial cells of untreated rats. In treated animals, intense T beta RII immunoreactivity was observed in epithelial cells, and a higher level of TGF beta mRNA was observed in both epithelial cells and stromal cells compared with control animals. In our opinion, the effect of epristeride on rat prostatic atrophy might be mediated via local growth factor(s).
Wu
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SF
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institute for Biological Science, Chinese Academy of Sciences, 294 Tai-yuan Road, Shanghai 200031, People's Republic of China.
Sun
H Z
HZ
Qi
X D
XD
Tu
Z H
ZH
D000728:Androgens / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008297:Male; D009919:Orchiectomy; D011467:Prostate / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000187:drug effects* / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000187:drug effects* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D000728:Androgens; D000730:Androstadienes; D004791:Enzyme Inhibitors; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C072547:epristeride; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1