PEROXIDASE AND EOSINOPHILS IN UTERINE ESTROGEN ACTION

这项研究的长期目标是进一步了解 雌激素在正常和肿瘤组织中作用的分子机制 生殖道的问题 本文的研究重点是第二次绑定 雌二醇的位置。 这种II型结合位点受雌激素调节， 对类固醇产生反应而增殖的组织。 这一近期目标 这项研究的目的是研究这些类型II的来源和性质， 结合位点。 对大鼠施用雌二醇导致特异性， 雌激素依赖性增加子宫内过氧化物酶的含量。 这种酶通过浸润性嗜酸性粒细胞转运到子宫内。 它 嗜酸性粒细胞也是 子宫II型结合位点，并且这些结合位点 嗜酸性粒细胞中的过氧化物酶 因此，嗜酸性粒细胞 将被分离和纯化，并测定两个II型结合位点 和过氧化物酶活性。 每种活性的亚细胞定位 将检查嗜酸性粒细胞的亚组织定位， II型结合位点和子宫内的过氧化物酶。 荷尔蒙 所有这三个监管也将被审查，以证明 相似或不同之处。 除了相关研究外， 过氧化物酶活性和II型结合位点的直接比较将 被执行。 纯化的过氧化物酶结合雌二醇的能力 当在II型试验中测定时，将有助于确定两种活性， 与一种蛋白质相关联。 本试验还将用于研究 II型结合和过氧化物酶的各种竞争剂和抑制剂 活动 这些嗜酸性粒细胞蛋白或其他可能的作用， 嗜酸性粒细胞因子将使用雌激素应答的人 子宫内膜癌细胞系 这些细胞也将用于研究 内源性II型配体在细胞调控中的作用 分裂和细胞死亡。 这些研究可能会开始阐明 在正常人和正常人中， 肿瘤组织

The long term objective of this research is to further the understanding of the molecular mechanism of estrogen action in normal and neoplastic tissue of the reproductive tract. This research is to focus on the second binding site for estradiol. This type II binding site is regulated by estrogens in tissue which proliferate in response to this steroid. The immediate goal of this research is to examine the source and nature of these type II binding sites. Estradiol administration to rats results in a specific, estrogen dependent increase in the uterine content of a peroxidase enzyme. This enzyme is transported into the uterus by infiltrating eosinophils. It is proposed in this application that the eosinophils are also the source of the uterine type II binding sites and further that these binding sites are the peroxidase enzyme found in the eosinophils. Therefore, eosinophils will be isolated and purified and assayed for both type II binding sites and peroxidase activity. The subcellular localization of each activity will be examined as well as the sub-tissue localization of the eosinophils, type II binding sites and the peroxidase in the uterus. The hormonal regulation of all three will also be examined in order to demonstrate similarities or differences. In addition to the correlative studies a direct comparison of the peroxidase activity and type II binding sites will be performed. The ability of the purified peroxidase to bind estradiol when assayed in the type II assay will help establish the two activities as being associated with one protein. This assay will also be used to study various competitors and inhibitors of type II binding and peroxidase activity. The possible role of these eosinophil proteins or other eosinophil factors will be examined using an estrogen responsive human endometrial carcinoma cell line. These cells will also be used to study the role of the endogenous ligand for type II in the control of cell division and cell death. These studies may begin to formulate a role of the eosinophils in the estrogen mediated growth response in both normal and neoplastic tissues.