Transforming growth factor-beta(s) and their receptors in aging rat prostate

Abstract

We hypothesize that rat fetal urogenital sinus mesenchyme (UGM) can induce prostatic growth of growth quiescent adult rat prostate through modulations of TGFbetas and their receptors. To test this hypothesis, prostatic ducts from aging rat prostate (4, 12, 17, 22, and 27 months) were combined with fetal rat UGM and grafted under renal capsule of athymic nude mice. At 1, 3, and 5 months the tissue recombinants were harvested from renal capsule and analyzed for their growth. The gene and protein expression of TGFbeta1, 2, 3 and their receptors, TbetaR-I and TbetaR-II, were analyzed by RT-PCR and immunohistochemistry, respectively. The results of these experiments demonstrate that prostate ducts when combined with rat UGM formed larger grafts as compared to control (prostatic ducts without UGM). The older rat prostate recombinants (17, 22, and 27 months) formed larger grafts (159 mg/graft) as compared to younger rat prostate (4 and 12 months) grafts (51 mg/graft). The mRNA and protein expression for TbetaR-I and TbetaR-II in 22 and 27 months rat prostate tissue recombinants were significantly lower than 4, 12, and 17 month tissue recombinants. However, mRNA expression for TGFbeta1, TGFbeta2, and TGFbeta3 did not change with aging rat tissue recombinants. The protein expression for TGFbeta1 was significantly up-regulated whereas TGFbeta2 and TGFbeta3 were down-regulated with aging prostate tissue recombinants. The present study demonstrates for the first time that rat fetal UGM differentially induces growth of aging rat prostate in a tissue recombinant model. The mechanisms of induction may be through up-regulation of TGFbeta1 and down-regulation of TGFbeta2, and TGFbeta3. However, the action of TGFbetas may be through TbetaR-I and TbetaR-II independent pathways since these receptors were lacking or low in older rat prostate tissue recombinants. These findings are important in understanding the mechanisms of UGM mediated prostatic growth.