The long term objective of these studies is to examine the steroid regulation of uterine function and further the understanding of the molecular mechanisms of estrogen regulation in normal and neoplastic tissue of the reproductive tract. Estradiol administration of rats results in a specific, estrogen dependent increase in the uterine content of leucocytes, and eosinophils in particular. There is a 50 fold increase in the number of uterine eosinophils as the animal leaves diestrus and enters estrus (150,000 vs 8,000,000). Similar steroid regulated leucocyte fluctuations are known to occur in the uteri of a variety of other species including the human. These observations have been known for over twenty years. However, the molecular mechanisms involved with this process are still not understood. This research will focus on the mechanisms of estrogen regulation of the infiltration of eosinophils and other blood cells into the rat uterus. The mechanism of eosinophil infiltration may represent one part of a more general response to estrogens. Thus we will apply some of the models and methods used to examine cellular infiltration in inflammation to the action of steroids in the reproductive tract. Our hypothesis is that the migration of the eosinophils into the uterus is due to chemotaxis. Furthermore, we propose that the uterus produces a chemotactic factor in response to hormone stimulation. The goals of the research therefore are to demonstrate the existence and biochemical nature of a uterine chemotactic factor. In addition, we plan to examine the hormonal regulation of this factor in terms of the kinetics and the requirement for receptor mediated genomic expression of the resident cells (epithelial, stromal, and myometrial cells). Lastly we propose to examine the ontogenic regulation of this response in relation to the ontogenic regulation of other uterine or inflammatory responses. To accomplish these goals we will use an """"""""in vitro"""""""" chemotactic assay with purified rat eosinophils as the target cell. The role eosinophils play in the uterus is unknown at present. However, due to the presence of collagenases and peroxidase they may envisaged to play a role in re-modeling the uterus either in preparation for, or after, pregnancy. These studies will begin to examine the regulation of leucocyte infiltration and thereby possibly begin to formulate a role for the eosinophils in the estrogen mediated growth response in both normal and neoplastic reproductive tissue.
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