ESTROGEN-INDUCED NORMAL AND DYSPLASTIC UTERINE GROWTH

当仓鼠接受人工合成的雌激素治疗时， 己烯雌酚（DES），他们的子宫始终表现出严重的 对雌激素的增生/肿瘤反应。 两种 另一种工作假设应该解释这种现象：1）直接 作用-新生儿的细胞生理学和/或组成 仓鼠子宫被DES损伤直接和永久地改变， 成人器官对雌激素的整体增殖反应 非典型，或2）间接作用-子宫营养活性由 雌激素主要通过或与其他未识别的 因素，新生儿DES治疗永久性地改变了水平或 这些因素的作用。 测试这些假设将开始 （具体目标#1）通过监测新生儿子宫的形态发生， 对照组和DES处理的供体动物， 对照和DES处理的成熟宿主的对侧颊囊， 要么保持原样，要么被剥夺雌激素，要么被取代。 到 确认和扩展的结果（具体目标#2），同型和 正常子宫间质和上皮异型重组 和DES处理的动物，并将其形态发生 研究：a）在体外使用补充有子宫组织的培养基 特定目标1中使用的相同宿主群的浸提液和/或血清 和B）体内（在颊囊内，使用与 具体目标#1。 最后（具体目标#3），北方印迹分析将 可以用来考虑两个基因表达的改变 原癌基因（c-myc和c-fos）可能参与了非典型的 暴露于DES的仓鼠子宫的雌激素反应性。 因为这种方法的组合依赖于很少的先验知识， 假设并适应体内和体外观察结果，公司 应该得出结论，哪个备选假设是最好的。 有效的. 这些信息应有助于长期 目的是了解雌激素如何调节子宫生长， 形态发生 这一目标在生物医学上很重要，因为：1） 成功的受孕和妊娠需要正常的子宫形态， 功能，和2）雌激素依赖性子宫肿瘤是负责 发病率和死亡率在当代美国社会相当高。

When hamsters are treated neonatally with the synthetic estrogen, diethylstilbestrol (DES), their uteri consistently exhibit a severe hyperplastic/neoplastic response to estrogen in adulthood. One of two alternative working hypotheses should explain this phenomenon: 1) Direct Action - The cellular physiology and/or composition of the neonatal hamster uterus is directly and permanently altered by the DES insult such that the adult organ's overall proliferative response to estrogen becomes atypical, or 2) Indirect Action - Uterotrophic activity is mediated by estrogen primarily through or in conjunction with other unidentified factors, and neonatal DES treatment permanently alters the level or functional activity of such factors. Testing these hypotheses will begin (Specific Aim # 1) by monitoring the morphogenesis of neonatal uteri from control and DES-treated donor animals that are transplanted into the contralateral cheek pouches of control and DES-treated mature hosts that are either left intact, estrogen-deprived or estrogen-replaced. To confirm and extend the findings (Specific Aim #2), homotypic and heterotypic recombination of uterine stroma and epithelium from control and DES-treated animals will be performed and their morphogenesis will be studied: a) in vitro using media supplemented with uterine tissue extracts and/or serum from the same host groups used in Specific Aim # 1 and b) in vivo (within the cheek pouch, using the same host groups as in Specific Aim #l. Lastly (Specific Aim #3), Northern blot analysis will be used to consider the possibility that altered expression of two proto-oncogenes (c-myc and c-fos) may be involved in the atypical estrogen responsiveness of uteri in neonatally DES-exposed hamsters. Because this combination of approaches relies on few, if any, a priori assumptions and accommodates both in vivo and in vitro observations, firm conclusions should be reached about which alternative hypothesis is most valid. Such information should contribute significantly to the long-term objective of understanding how estrogen regulates uterine growth and morphogenesis. This objective is biomedically important because: 1) successful conception and gestation demands normal uterine form and function, and 2) estrogen-dependent uterine neoplasms are responsible for considerable morbidity and mortality in contemporary American society.