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ORIGINAL ARTICLE

Effect of Epristeride on the Expression of IGF-1 and TGF-ß Receptors in Androgen-Induced Castrated Rat Prostate

Shu-Fang Wu^*,2, Hong-Zhi Sun^,2, Xiao-Dong Qi^* and Zeng-Hong Tu^*,1

^* 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; and
Medical Center of Fudan University, Shanghai 200032, People's Republic of China

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 ß (TGFß) are thought important in regulating prostate growth and homeostasis, and their expression undergoes changes in proliferative prostatic disease. Epristeride, a 5-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-ß1 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 TGFß receptors at the protein level and TGFß at the mRNA level were found in the prostatic hyperplastic epithelial cells of untreated rats. In treated animals, intense TßRII immunoreactivity was observed in epithelial cells, and a higher level of TGFß 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).

Key Words: epristeride • rat prostate • growth factor • immunohistochemistry • in situ hybridization

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