Yamashita Shuji
Electron Microscope Laboratory, School of Medicine, Keio University, 35-Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Curr Pharm Des. 2006;12(12):1505-20. doi: 10.2174/138161206776389840.
Neonatal diethylstilbestrol (DES) exposure elicits a wide range of abnormalities in the female mouse genital tract. This animal model system is suitable for investigating the mechanism of DES syndrome in humans. Accumulated evidence has shown that critical periods in development are present for distinct and permanent alterations in the female genital tract of mice exposed to DES neonatally (DES-mice). These effects of DES and other estrogens are mainly mediated by estrogen receptor alpha (ER alpha) through multiple pathways. Induction of ER alpha by DES exposure in neonatal stromal and epithelial cells, and successive premature activation of estrogen-regulated genes are thought to be essential to induce the abnormalities. Induction of malformation, permanent changes in estrogen-regulated genes, such as protooncogenes and growth factors, and carcinogenesis are assumed to be interdependent. This review focuses the following topics to discuss the molecular basis of DES-induced abnormalities mainly based on the results by histochemical techniques in the uterus: spatiotemporal expression of ER alpha and coactivators, proteins relating morphogenesis, and estrogen-regulated protooncogenes and growth factors.
新生儿接触己烯雌酚（DES）会引发雌性小鼠生殖道出现多种异常。这个动物模型系统适用于研究人类DES综合征的发病机制。越来越多的证据表明，对于新生期接触DES的小鼠（DES小鼠），其雌性生殖道存在不同且永久性改变的关键发育时期。DES和其他雌激素的这些作用主要通过雌激素受体α（ERα）经多种途径介导。在新生期基质和上皮细胞中，DES暴露诱导ERα表达，以及随后雌激素调节基因的过早激活被认为是诱导异常的关键。畸形的诱导、雌激素调节基因（如原癌基因和生长因子）的永久性改变以及致癌作用被认为是相互依存的。本综述聚焦以下主题，主要基于子宫组织化学技术的结果来探讨DES诱导异常的分子基础：ERα和共激活因子的时空表达、与形态发生相关的蛋白质，以及雌激素调节的原癌基因和生长因子。
