PEROXIDASE AND EOSINOPHILS IN UTERINE ESTROGEN ACTION

这项研究的长期目标是加深对 雌激素在正常组织和肿瘤组织中作用的分子机制 生殖道的。本研究的重点是二次捆绑 雌二醇的位置。这个II型结合位点是由雌激素调节的 对这种类固醇有反应而增殖的组织。眼前的目标 这项研究的目的是检查这些类型II的来源和性质 结合部位。给大鼠服用雌二醇会导致一种特定的， 雌激素依赖性子宫中一种过氧化物酶含量的增加。 这种酶通过渗透嗜酸性粒细胞进入子宫。它 在本申请中提出，嗜酸性粒细胞也是 子宫II型结合部位，而且这些结合部位是 嗜酸性粒细胞中发现的过氧化物酶。因此，嗜酸性粒细胞 将被分离和纯化，并对两个II型结合位点进行检测 和过氧化物酶活性。每种活动的亚细胞定位 将被检查以及嗜酸性粒细胞的亚组织定位， 子宫中的II型结合部位和过氧化物酶。荷尔蒙 还将研究所有这三个方面的监管，以证明 相似或不同之处。除了相关的研究外， 过氧化物酶活性和II型结合位点的直接比较将 被执行。纯化的过氧化物酶与雌二醇的结合能力 当在II型化验中进行化验时，将有助于确定这两种活动为 与一种蛋白质有关。这项测试也将被用于研究 II型结合和过氧化物酶的各种竞争对手和抑制剂 活动。这些嗜酸性粒细胞蛋白或其他 嗜酸性粒细胞因子将使用对雌激素有反应的人进行检测 子宫内膜癌细胞株。这些细胞也将被用于研究 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制定一个角色 雌激素中的嗜酸性粒细胞介导正常和 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.