PEROXIDASE AND EOSINOPHILS IN UTERINE ESTROGEN ACTION

已显示，雌二醇可与靶细胞中的特异性受体相互作用， 细胞，从而刺激基因表达。 细胞培养 模型（例如，人类乳腺癌细胞系）已经使 对了解相关分子机制的贡献 在这个过程中。 然而，体内反应更复杂，因为 反应组织如子宫由至少三种 常驻细胞类型（上皮、基质和子宫肌层）， 对类固醇有不同的反应 而且 给大鼠施用雌二醇会产生一种特定的雌激素， 白细胞，特别是嗜酸性粒细胞进入子宫的依赖性流入。 嗜酸性粒细胞的数量大约增加了50倍 在雌二醇刺激后的子宫中。 这种增加 已经证明通过大鼠的正常发情周期进行调节 在发情期，嗜酸性粒细胞从低的8，000，000达到最大值， 间情期15万。 类似的增加也出现在产后 子宫 嗜酸性粒细胞趋化因子的存在已被证实是一种新的趋化因子。 在子宫内记录（ECF-U）。 这个因子是由雌激素刺激的 通过受体介导的机制，并通过 孕激素和糖皮质激素的相互作用。 拟议研究 将集中在两个方面关于这个趋化因子。 第一、 将对ECF-U的性质进行审查，这将通过以下方式完成： ECF-U的分离、鉴定及克隆 cDNA。 第二，细胞起源和分子机制， 将检测ECF-U表达的调节。 的渗透 嗜酸性粒细胞，如哮喘患者的肺，已经被 与上皮细胞损伤或死亡相关。 在生殖 束嗜酸性粒细胞或嗜酸性粒细胞同源蛋白已经与 在正常的大鼠动情周期中组织重塑， 着床和产后子宫退化。 我们假设 子宫嗜酸性粒细胞在组织重塑中发挥作用。这 将通过检查子宫的生长和功能来检验这一假设。 无嗜酸性粒细胞浸润。 嗜酸性粒细胞的浸润 用中和抗体治疗大鼠， ECF-U阻止趋化性。 这些研究将导致一个声音 了解ECF-U的性质和控制机制， 嗜酸性粒细胞浸润。 他们还将提供新的信息， 子宫功能调节及激素调节机制 在一个综合系统中。

Estradiol, has been shown to interact with specific receptors in target cells resulting in the stimulation of gene expression. Cell culture models (eg. human breast cancer cell lines) have made valued contributions to the understanding of the molecular mechanisms involved in this process. However, in vivo responses are more complicated since responsive tissues such as the uterus are composed of at least three resident cell types (epithelial, stromal and myometrial) each of which can express different responses to steroids. Furthermore, the administration of estradiol to rats results in a specific, estrogen dependent influx of leukocytes, especially eosinophils into the uterus. There is approximately a 50 - fold increase in the number of eosinophils in the uterus following stimulation with estradiol. This increase has been shown to be regulated through the normal estrous cycle of the rat reaching a maximum of 8,000,000 eosinophils at estrus from a low of 150,000 at diestrus. Similar increases have been seen in the post-partum uterus. The presence of an eosinophil chemotactic factor has been documented in the uterus (ECF-U). This factor is stimulated by estrogens through a receptor mediated mechanism and further regulated through the interaction of progestins and glucocorticoids. The proposed research will focus on two aspects regarding this chemotactic factor. Firstly, the nature of ECF-U will be examined, this will be accomplished through the isolation and characterization of the factor and cloning of ECF-U cDNA. Secondly, the cellular origin and molecular mechanisms of regulation of ECF-U expression will be examined. The infiltration of eosinophils, as in the case of lungs of patients with asthma, has been associated with epithelial cell damage or death. In the reproductive tract eosinophils or eosinophil homologous proteins have been associated with tissue remodeling during; the normal rat estrous cycle, implantation, and regression of the post-partum uterus. We hypothesize that uterine eosinophils play a role in tissue remodeling. This hypothesis will be tested by examining uterine growth and function in the absence of eosinophil infiltration. The infiltration of eosinophils will be prevented by treatment of rats with neutralization antibodies against ECF-U which prevent chemotaxis. These studies will result in a sound understanding of the nature of ECF-U and the mechanisms which control eosinophil infiltration. They will also provide new information as to the regulation of uterine function and mechanisms of steroid regulation in an integrated system.