Endometrial hyperplasia and apoptosis following neonatal diethylstilbestrol exposure and subsequent estrogen stimulation in both host and transplanted hamster uteri.
Endometrial hyperplasia and apoptosis following neonatal diethylstilbestrol exposure and subsequent estrogen stimulation in both host and transplanted hamster uteri.
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发表时间：
1997-05
期刊：
影响因子：
11.2
通讯作者：
W. Hendry;X. Zheng;W. W. Leavitt-W.;W. Branham;D. Sheehan
中科院分区：
文献类型：
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作者：
W. Hendry;X. Zheng;W. W. Leavitt-W.;W. Branham;D. Sheehan
产前暴露于合成雌激素己烯雌酚（DES）导致人类生殖道的形态发生改变和肿瘤。在仓鼠中，新生儿DES暴露改变了早期子宫形态发生，并诱导成人子宫内膜腺癌。我们现在证明，这种现象在仓鼠的癌前阶段反映了异常的子宫反应雌激素的特点是增生性病变的子宫内膜上皮细胞，包括免疫和/或炎症成分。有趣的是，生物化学和原位分析显示，增生上皮也是细胞凋亡导致细胞死亡的活性部位。为了进一步探索这种现象的机制，将来自7日龄对照或DES暴露供体的子宫移植到对照或暴露于DES的成年宿主的颊囊中，并对两个宿主组进行处理以提供高循环水平的雌二醇。在四种异位情况中，组织病理学病变（上皮增生、发育异常和凋亡）几乎完全分离到由子宫内DES暴露的子宫组成的两种情况。移植到DES宿主的对照子宫中几乎没有病变，排除了宿主全身因素作为致病因子。因此，我们得出结论，DES或其代谢物改变细胞生理学和/或组成的发展中的子宫（启动事件），以这样的方式，它此后异常响应雌激素刺激（促进事件）。这些观察结果用于进一步定义一个独特的实验系统，用于探测：（a）临床“DES综合征”的各个方面;（B）雌激素如何调节正常子宫生长和形态发生;和（c）该过程如何退化为不受调节的肿瘤状态。
Prenatal exposure to the synthetic estrogen diethylstilbestrol (DES) causes morphogenetic alterations and neoplasia in the human reproductive tract. In the hamster, neonatal DES exposure alters early uterine morphogenesis and induces endometrial adenocarcinomas in adults. We now demonstrate that the preneoplastic stages of this phenomenon in the hamster reflect an abnormal uterotropic response to estrogen that is characterized by hyperplastic lesions in the endometrial epithelium and includes an immune and/or inflammatory component. Interestingly, biochemical and in situ analysis revealed that the hyperplastic epithelium is also an active site of cell death by apoptosis. To further probe the mechanism of this phenomenon, uteri from 7-day-old control or DES-exposed donors were transplanted into the cheek pouches of control or neonatally DES-exposed adult hosts, and both host groups were treated to provide high circulating levels of estradiol. Among the four ectopic scenarios, histopathological lesions (epithelial hyperplasia, dysplasia, and apoptosis), segregated almost exclusively to the two that consisted of neonatally DES-exposed uteri. The virtual absence of lesions in control uteri transplanted to DES hosts eliminated host systemic factors as causative agents. Therefore, we conclude that DES or its metabolites alter the cellular physiology and/or composition of the developing uterus (initiating event) in such a way that it thereafter responds abnormally to estrogenic stimulation (promoting event). These observations serve to further define a unique experimental system for probing: (a) various aspects of the clinical "DES Syndrome"; (b) how estrogen regulates normal uterine growth and morphogenesis; and (c) how this process can degenerate to the unregulated neoplastic state.