PEROXIDASE AND EOSINOPHILS IN UTERINE ESTROGEN ACTION

这些研究的长期目标是检查类固醇 子宫功能的调节及对子宫功能的进一步认识 正常和雌性激素调节的分子机制 生殖道的肿瘤组织。雌二醇 大鼠给药后会产生一种特定的、雌激素依赖的 子宫内白细胞、嗜酸性粒细胞含量增加 很特别。子宫的数量增加了50倍。 动物离开发情期进入发情期时的嗜酸性粒细胞 (150,000比800,000)。类固醇调节的白细胞 已知的波动发生在各种其他类型的子宫中 包括人类在内的物种。这些观察结果已为人所知 已经有二十多年了。然而，其中涉及的分子机制 关于这一过程目前还不清楚。这项研究将 关注雌激素对渗透的调节机制 嗜酸性粒细胞和其他血细胞进入大鼠子宫。这个 嗜酸性粒细胞渗入的机制可能代表了 对雌激素的更普遍的反应。因此，我们将应用一些 用于研究细胞渗透的模型和方法 生殖道中类固醇作用引起的炎症。 我们的假设是，嗜酸性粒细胞迁移到 子宫是由于趋化作用所致。此外，我们建议 子宫对激素的反应产生趋化因子 刺激。因此，研究的目标是 证明子宫的存在和生化性质 趋化因子。此外，我们计划检查荷尔蒙 这一因素的调节从动力学和 受体介导的基因表达的要求 常驻细胞(上皮细胞、间质细胞和肌层细胞)。最后一点 我们建议研究这种反应的个体调控在 与其他子宫或卵巢的个体调控的关系 炎症反应。为了实现这些目标，我们将使用 以纯化大鼠嗜酸粒细胞为靶细胞的体外趋化试验 目标单元格。嗜酸性粒细胞在子宫中的作用尚不清楚。 目前。然而，由于胶原酶的存在和 过氧化物酶，他们可以设想在重新建模过程中发挥作用 准备怀孕或怀孕后的子宫。这些 研究将开始检查白细胞的调节 渗透，从而可能开始制定一个角色，为 嗜酸性粒细胞在雌激素介导的生长反应中的作用 和肿瘤生殖组织。

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.