PEROXIDASE AND EOSINOPHILS IN UTERINE ESTROGEN ACTION

雌二醇已被证明与靶标中的特定受体相互作用 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）已取得了宝贵的成果 对理解所涉及的分子机制的贡献 在这个过程中。 然而，体内反应更为复杂，因为 子宫等反应组织至少由三个组成 常驻细胞类型（上皮细胞、基质细胞和肌层细胞） 可以对类固醇表达不同的反应。 此外， 给大鼠注射雌二醇会产生一种特定的雌激素 白细胞，尤其是嗜酸性粒细胞依赖地流入子宫。 嗜酸性粒细胞数量大约增加50倍 雌二醇刺激后在子宫中。 这一增加有 已被证明通过大鼠的正常动情周期进行调节 发情期嗜酸性粒细胞从最低达到最高 8,000,000 发情间期有 150,000 个。 产后也出现了类似的增长 子宫。 嗜酸性粒细胞趋化因子的存在 记录在子宫内（ECF-U）。 该因子受雌激素刺激 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。 拟议的研究 将重点关注有关该趋化因子的两个方面。 首先， ECF-U 的性质将受到审查，这将通过 ECF-U因子的分离和表征以及克隆 cDNA。 其次，细胞起源和分子机制。 将检查ECF-U表达的调节。 的渗透 嗜酸性粒细胞，就像哮喘患者肺部的情况一样， 与上皮细胞损伤或死亡有关。 在生殖方面 道嗜酸性粒细胞或嗜酸性粒细胞同源蛋白已相关 期间发生组织重塑；正常大鼠动情周期， 植入和产后子宫退化。 我们假设 子宫嗜酸性粒细胞在组织重塑中发挥作用。这个 该假设将通过检查子宫生长和功能来检验 无嗜酸性粒细胞浸润。 嗜酸性粒细胞的浸润会 通过用中和抗体治疗大鼠来预防 ECF-U 可防止趋化作用。 这些研究将产生良好的结果 了解 ECF-U 的性质及其控制机制 嗜酸性粒细胞浸润。 他们还将提供有关以下方面的新信息： 子宫功能的调节和类固醇调节的机制 在一个集成的系统中。

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.