PEROXIDASE AND EOSINOPHILS IN UTERINE ESTROGEN ACTION

雌二醇，已被证明与靶组织中的特定受体相互作用 导致基因表达受到刺激的细胞。细胞培养 模型(例如人类乳腺癌细胞株)已经成为有价值的 对理解所涉及的分子机制的贡献 在这个过程中。然而，体内的反应更复杂，因为 子宫等有反应的组织至少由三部分组成。 驻留细胞类型(上皮细胞、间质细胞和肌层细胞) 对类固醇有不同的反应。此外， 给大鼠注射雌二醇会产生一种特殊的雌激素 白血球，尤其是嗜酸性粒细胞依赖地流入子宫。 嗜酸性粒细胞的数量大约增加了50倍 在雌二醇刺激下的子宫内。这一增长已经 已被证明通过正常的大鼠发情周期进行调节 发情期最多可达8,000,000个嗜酸性粒细胞 发情期15万头。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 记录在子宫中(ECF-U)。这种因子是由雌激素刺激的。 通过受体介导的机制，并进一步通过 孕激素和糖皮质激素的相互作用。拟议的研究 将重点关注关于这种趋化因子的两个方面。首先， 将研究ECF-U的性质，这将通过以下方式完成 ECF-U因子的分离、鉴定及克隆 CDNA.其次，细胞起源和分子机制的研究。 本课程将研究ECF-U表达的调控。……的渗透 嗜酸性粒细胞，就像哮喘患者的肺一样，已经被 与上皮细胞损伤或死亡有关。在生殖方面 嗜酸性粒细胞或嗜酸性粒细胞同源蛋白已被关联 在正常的大鼠发情周期中有组织重塑， 植入，产后子宫退化。我们假设 子宫嗜酸性粒细胞在组织重塑中起作用。这 假说将通过检查子宫生长和功能来检验 未见嗜酸性粒细胞渗入。嗜酸性粒细胞的渗透会 通过用中和抗体治疗大鼠来预防 阻止趋化的ECF-U。这些研究将产生一个健全的 对ECF-U的性质和控制机制的理解 嗜酸性粒细胞渗入。他们还将提供有关以下方面的新信息 子宫功能的调节与类固醇调节机制 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.