Evidence that epithelial and mesenchymal estrogen receptor-α mediates effects of estrogen on prostatic epithelium
Evidence that epithelial and mesenchymal estrogen receptor-α mediates effects of estrogen on prostatic epithelium
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DOI：
10.1006/dbio.2000.9994
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发表时间：
2001-01-15
影响因子：
2.7
通讯作者：
Cunha, G
中科院分区：
文献类型：
--
作者：
Risbridger, G;Wang, H;Cunha, G
雌激素与雄激素结合可诱导前列腺的异常生长和恶性肿瘤。雌激素作用通过两种受体亚型介导：雌激素受体α（ER α）和β（ER β）。用合成雌激素己烯雌酚（DES）处理缺乏功能性ER α（α ERKO）或ER β（β ERKO）的野生型（wt）和转基因小鼠。DES在野生型和β ERKO小鼠中诱导前列腺鳞状上皮化生（SQM），但在α ERKO小鼠中不诱导，表明ER α在诱导前列腺上皮SQM中起重要作用，而非ERP。为了确定上皮和间质ER α在该应答中的各自作用，用来自wt和ERKO小鼠的前列腺上皮（E）和间质（S）构建以下组织重组体：wt-S+wt-E、α ERKO-S+ α ERKO-E、wt-S+ α ERKO-E和（α ERKO-S+wt-E）。在wt-St-wt-E组织重组体中观察到对DES的化生反应。DES的这种反应涉及基底上皮细胞的多层化，细胞角蛋白10的表达和孕酮受体的上调。含有α ERKO-E和/或-S（α ERKO-S + α ERKO-E、wt-S+ α ERKO-E和α ERKO-S+wt-E）的组织重组体对DES无反应。因此，完整和均匀的上皮SQM需要上皮和基质中的ER α。这些结果提供了一个新的洞察细胞间的相互作用介导的雌激素作用在前列腺通过ER α。(C)北京：科学出版社.
In combination with androgens, estrogens can induce aberrant growth and malignancy of the prostate gland. Estrogen action is mediated through two receptor subtypes: estrogen receptors alpha (ER alpha) and beta (ER beta). Wild-type (wt) and transgenic mice lacking a functional ER alpha (alpha ERKO) or ER beta (beta ERKO) were treated with the synthetic estrogen diethylstilbestrol (DES). DES induced prostatic squamous metaplasia (SQM) in wt and beta ERKO but not in alpha ERKO mice, indicating an essential role for ER alpha, but not ERP, in the induction of SQM of prostatic epithelium. In order to determine the respective roles of epithelial and stromal ER alpha in this response, the following tissue recombinants were constructed with prostatic epithelia (E) and stroma (S) from wt and ERKO mice: wt-S+wt-E, alpha ERKO-S+alpha ERKO-E, wt-S+alpha ERKO-E, and (alpha ERKO-S+wt-E. A metaplastic response to DES was observed in wt-St-wt-E tissue recombinants. This response to DES involved multilayering of basal epithelial cells, expression of cytokeratin 10, and up-regulation of the progesterone receptor. Tissue recombinants containing (alpha ERKO-E and/or -S (alpha ERKO-S+alpha ERKO-E, wt-S+alpha ERKO-E, and alpha ERKO-S+wt-E) failed to respond to DES. Therefore, full and uniform epithelial SQM requires ER alpha in the epithelium and stroma. These results provide a novel insight into the cell-cell interactions mediating estrogen action in the prostate via ER alpha. (C) 2001 Academic Press.