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).