PEROSIDASE AND EOSINOPHILS IN UTERINE ESTROGEN ACTION

本研究的长期目标是进一步了解

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.