ROLE OF RECEPTORS IN ESTROGEN ACTION IN THE UTERUS

受体在子宫雌激素作用中的作用

• 批准号: 3313134
• 负责人: EUGENE R DE-SOMBRE
• 金额: $ 21.66万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-08-01 至 1986-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3313134
• 关键词: autoradiography; chromatin; gel electrophoresis; gel filtration chromatography; gene expression; genetic regulation; glucocorticoids; growth /development; hormone regulation /control mechanism; molecular pathology; progestins; radiotracer; scintillation spectrometry; uterus

The long term objective of this research is to understand the role of estrogen receptors in the regulation of uterine growth and function by elucidating the important receptors mediated events which are required for estrogen regulation of gene function in target cells. This is to be accomplished by the study of the steroid hormone regulated expression of the marker protein, peroxidase, correlated with estrogen-dependent receptor modulation and chromatin binding and by this means to discover the biologically important details of estrogen action at the molecular level. The plan of attack is to use several experimental systems in the rat, mouse, and hamster and various biologically meaningful hormone treatment protocols to discover the nature of hormonal controls of peroxidase expression, and to relate these changes in marker with the estrogen receptor interaction and its activation, nuclear binding, and chromatin localization, and eventually gene regulation. With antibody to rat uterine peroxidase we will embark on studies to quantitate the hormonal regulation of peroxidase mRNA, immunochemically detectable peroxidase polypeptide and enzyme in order to clarify the nature of the transcriptional, processing, translational and post-translational controls effected by hormones in the uterus. With the newly developed reagents in our laboratory, specifically antibody to the marker peroxidase and antibodies to the estrogen receptor, we have the unique reagents and capability to carry out studies which can clarify the intimate details of the estrogen receptor-mediated regulation of gene expression in the mammalian reproductive tract. These studies can be expected to improve our understanding of the endocrinology of the uterus at the biochemical level.

这项研究的长期目标是了解 雌激素受体在子宫生长和功能调节中的作用 阐明重要的受体介导的事件所需的 雌激素对靶细胞基因功能的调节。这将是 通过类固醇激素调节表达的研究完成 与雌激素依赖受体相关的标记蛋白过氧化物酶 调制和染色质结合，并通过这种方法发现 在分子水平上雌激素作用的重要生物学细节。 攻击计划是在老鼠身上使用几个实验系统， 小鼠、仓鼠和各种具有生物意义的激素治疗 发现过氧化物酶荷尔蒙控制性质的方案 表达，并将这些标志物的变化与雌激素联系起来 受体相互作用及其激活、核结合和染色质 本地化，最终实现基因调控。用抗大鼠子宫抗体 我们将着手研究如何量化激素的调节。 过氧化物酶mRNA、免疫化学可检测的过氧化物酶多肽和 为了阐明酶的转录、加工的性质， 荷尔蒙对翻译和翻译后控制的影响 子宫。与我们实验室新开发的试剂，特别是 标记过氧化物酶的抗体和雌激素受体的抗体， 我们有独特的试剂和能力进行研究，可以 阐明雌激素受体介导的调节的密切细节 哺乳动物生殖道中的基因表达。这些研究可以 有望提高我们对子宫内分泌学的理解 在生化水平上。