Experimental diabetes-induced regression of the rat prostate is associated with an increased expression of transforming growth factor-β
Experimental diabetes-induced regression of the rat prostate is associated with an increased expression of transforming growth factor-β
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DOI：
10.1016/s0022-5347(05)67491-5
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发表时间：
2000-07-01
影响因子：
6.6
通讯作者：
Latifpour, J
中科院分区：
文献类型：
--
作者：
Ikeda, K;Wada, Y;Latifpour, J
目的：转化生长因子-β(转化生长因子-β)是一种强有力的细胞生长抑制因子，通过复杂的生长因子网络在前列腺癌雄激素依赖过程中发挥重要作用。转化生长因子-β在前列腺中的表达受到雄激素的负调控。由于实验性糖尿病导致大鼠前列腺退行性变和血清睾酮水平下降，我们检测了糖尿病大鼠前列腺中转化生长因子-β1和转化生长因子-β2的mRNA和蛋白水平的变化。材料和方法：采用相对多重RT-PCR、半定量Western blotting和免疫组织化学方法，研究了链脲佐菌素(STZ)诱导的糖尿病大鼠、胰岛素治疗的糖尿病大鼠和年龄匹配的对照组大鼠前列腺中转化生长因子-β1和转化生长因子-β2及其各自的mRNAs的表达。糖尿病大鼠前列腺组织中转化生长因子-β1、转化生长因子-β2的mRNA和蛋白表达均上调。胰岛素治疗使观察到的前列腺重量和血清睾酮水平的变化正常化，并将转化生长因子-β1和转化生长因子-β2在基因转录和蛋白水平的表达逆转至对照水平。免疫组织化学研究表明，转化生长因子-β1定位于前列腺间质细胞，而转化生长因子-β2表达于上皮和间质细胞。结论：转化生长因子-β1和转化生长因子-β2可能参与了糖尿病引起的前列腺退行性变。
Purpose: 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.Materials and Methods: The expression of TGF-beta 1 and TGF-beta 2 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.Results: Induction of diabetes caused a significant reduction in prostatic weight and in serum testosterone levels in rats. Both mRNA and protein levels of TGF-beta 1, and mRNA level of TGF-beta 2 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-beta 1 and TGF-beta 2 expression at the gene transcript and protein levels to control levels. Immunohistochemical studies demonstrated that TGF-beta 1 is localized to prostatic stromal cells, whereas TGF-beta 2 is located in both epithelial and stromal cells.Conclusion: These results suggest that TGF-beta 1 and TGF-beta 2 may be involved in the diabetes-induced regression of the prostate gland.