Effect of epristeride on the expression of IGF-1 and TGF-beta receptors inandrogen-induced castrated rat prostate

The development of benign prostatic hyperplasia (BPH) is an androgen-depend ent process that may be mediated by a number of locally produced growth fac tors. Among them, insulinlike growth factor 1 (IGF-1) and transforming grow th factor beta (TGF beta) are thought important in regulating prostate grow th and homeostasis, and their expression undergoes changes in proliferative prostatic disease. Epristeride, a 5 alpha -reductase inhibitor, is an, eff ective drug in the treatment of BPH, inducing regressive changes in the pro state. This study was designed to assess the effects, of epristeride on exp ression of these two factors at mRNA and protein levels in castrated rats m aintained with exogenous testosterone. Epristeride treatment caused signifi cant reduction in ventral prostate weight in a dose-dependent manner. There was a positive correlation between IGF-1 mRNA expression and ventral prost ate weight and an inverse, correlation between TGF-beta1 mRNA expression an d ventral prostate. weight. Immunohistochemistry showed strong IGF-1 recept or immunoreactivity in the prostatic epithelial cells of untreated animals. In situ hybridization demonstrated high levels, of IGF-1 mRNA expression b oth in the prostatic stromal and epithelial cells, of untreated rats. In tr eated rats, both IGF-1 receptor protein and; IGF-1 mRNA levels decreased si gnificantly, and IGF-1 mRNA was mainly expressed in prostatic stromal cells . Weak expression; of TGF beta receptors at the protein level and TWO at th e mRNA level were found in the prostatic hyperplastic epithelial cells of u ntreated rats. In treated animals, intense T beta RII immunoreactivity was, observed in epithelial cells, and a higher level of TGF beta mRNA was obse rved in both epithelial cells and stromal cells compared with control anima ls. In our opinion, the effect of epristeride on rat prostatic, atrophy mig ht be mediated via local growth factor(s).