EXPERIMENTAL DIABETES-INDUCED REGRESSION OF THE RAT PROSTATE IS ASSOCIATED WITH AN INCREASED EXPRESSION OF TRANSFORMING GROWTH FACTOR-β

Abstract

Transforming growth factor-beta (TGF-beta), a potent inhibitor of cell growth, plays an important role in the androgen-dependent processes of the prostate through a complex network of growth factors. TGF-beta expression in the prostate is under negative regulatory control of androgen. As experimental diabetes causes a regression of the prostate and decrease in serum testosterone levels in rats, we examined TGF-beta alterations at the mRNA and protein levels in the diabetic rat prostate. The expression of TGF-beta1 and TGF-beta2 and their respective mRNAs in prostates from streptozotocin (STZ)-induced diabetic, insulin-treated diabetic and age-matched control rats were investigated, using relative multiplex RT-PCR, semi-quantitative Western blotting, and immunohistochemistry. Induction of diabetes caused a significant reduction in prostatic weight and in serum testosterone levels in rats. Both mRNA and protein levels of TGF-beta1, and mRNA level of TGF-beta2 were up-regulated in the diabetic rat prostate. Insulin-treatment normalized changes observed in prostatic weight and serum testosterone levels, and reversed the alterations in the TGF-beta1 and TGF-beta2 expression at the gene transcript and protein levels to control levels. Immunohistochemical studies demonstrated that TGF-beta1 is localized to prostatic stromal cells, whereas TGF-beta2 is located in both epithelial and stromal cells. These results suggest that TGF-beta1 and TGF-beta2 may be involved in the diabetes-induced regression of the prostate gland.