Vitkus Spencer, Yeh Chiuan-Ren, Lin Hsiu-Hsia, Hsu Iawen, Yu Jiangzhou, Chen Ming, Yeh Shuyuan
Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, New York 14642, USA.
Mol Endocrinol. 2013 Jan;27(1):38-49. doi: 10.1210/me.2012-1212. Epub 2012 Nov 30.
Estrogen signaling, through estrogen receptor (ER)α, has been shown to cause hypertrophy in the prostate. Our recent report has shown that epithelial ERα knockout (KO) will not affect the normal prostate development or homeostasis. However, it remains unclear whether ERα in different types of stromal cells has distinct roles in prostate development. This study proposed to elucidate how KO of ERα in the stromal smooth muscle or fibroblast cells may interrupt cross talk between prostate stromal and epithelial cells. Smooth muscle ERαKO (smERαKO) mice showed decreased glandular infolding with the proximal area exhibiting a significant decrease. Fibroblast ERαKO mouse prostates did not exhibit this phenotype but showed a decrease in the number of ductal tips. Additionally, the amount of collagen observed in the basement membrane was reduced in smERαKO prostates. Interestingly, these phenotypes were found to be mutually exclusive among smERαKO or fibroblast ERαKO mice. Compound KO of ERα in both fibroblast and smooth muscle showed combined phenotypes from each of the single KO. Further mechanistic studies showed that IGF-I and epidermal growth factor were down-regulated in prostate smooth muscle PS-1 cells lacking ERα. Together, our results indicate the distinct functions of fibroblast vs. smERα in prostate development.
雌激素信号通过雌激素受体(ER)α已被证明会导致前列腺肥大。我们最近的报告显示,上皮细胞ERα基因敲除(KO)不会影响前列腺的正常发育或内环境稳定。然而,尚不清楚不同类型基质细胞中的ERα在前列腺发育中是否具有不同作用。本研究旨在阐明基质平滑肌或成纤维细胞中ERα基因敲除如何中断前列腺基质细胞与上皮细胞之间的相互作用。平滑肌ERα基因敲除(smERαKO)小鼠的腺体褶皱减少,近端区域显著减少。成纤维细胞ERα基因敲除小鼠的前列腺未表现出这种表型,但导管末端数量减少。此外,smERαKO前列腺基底膜中观察到的胶原蛋白量减少。有趣的是,这些表型在smERαKO或成纤维细胞ERαKO小鼠中是相互排斥的。成纤维细胞和平滑肌中ERα的复合基因敲除显示出每种单基因敲除的综合表型。进一步的机制研究表明,在缺乏ERα的前列腺平滑肌PS-1细胞中,IGF-I和表皮生长因子下调。总之,我们的结果表明成纤维细胞与smERα在前列腺发育中具有不同功能。