ENDOMETRIUM GENE REGULATION DURING DECIDUALIZATION

这项研究的长期目标是确定 转录因子在子宫内膜细胞蜕膜过程中的表达。 我们假设有几个转录因子调节 下游靶基因激活与蜕膜瘤的发生 胚胎，并维持多样化的生物学功能 怀孕了。为了继续这项拟议的研究，人类子宫内膜细胞培养 它概括了体内蜕膜化的过程 已经成立了。利用这个系统，我们已经阐明了孕激素诱导的 产生胰岛素样生长因子结合蛋白-1(IGFBP-1)， 蜕膜细胞的主要分泌蛋白。我们还确认了 IGFBP-1基因启动子中的基本顺式元件。这些 顺式元件为分析蜕膜功能提供了分子工具 细胞转录因子。拟议的研究有四个具体目标： 目标1将鉴定和表征转录因子 调节IGFBP-1基因的激活。这项研究将集中在 C/TCAAT、Cre、Sp1和Sp1结合蛋白的作用方式 前基序的GATA基序和孕激素受体(PR)。目标2将 确定AIM中描述的转录因子的功能 1、在催乳素(PRL)、孕激素受体(PR)和纤维连接蛋白(FN)启动子中 基质/蜕膜。目标3将确定这些转录因子如何 作用于内源性基因IGFBP-1、PRL、PR和FN。目标4将 确定雌激素、黄体酮和合成类固醇的作用， 激动剂/拮抗剂对功能转录mRNA水平的影响 各种因素。建议的研究结果将有助我们 了解转录因子是如何控制 人子宫内膜间质/蜕膜细胞的蜕膜化。这 信息可以用来改善生育调控， 组织特异性生育控制，植入失败的治疗和 妊娠障碍。

The long-term goal of this study is to determine the function of transcription factors expressed during endometrial cell decidualization. We hypothesize that a handful of transcription factors regulate the downstream target gene activation to develop deciduoma receptive to the embryo and to maintain diversified biological functions during pregnancy. To pursue the proposed study, human endometrial cell culture which recapitulates the process of decidualization in vivo has been established. Using this system we have elucidated the progestin-induced production of insulin-like growth factor binding protein-1 (IGFBP-1), the major secretory protein of decidual cells. We have also identified the essential cis-elements in the promoter of the, IGFBP-1 gene. These cis-elements provide molecular tool to analyze the functions of decidual cell transcription factors. The proposed study has four specific aims: Aim 1 will identify and characterize the transcription factors that regulate the activation of the IGFBP-1 gene. The study will focus on the modes of action of the binding proteins of C/TCAAT, CRE , Sp1 and GATA motifs and progesterone receptor (PR) of PRE motif. Aim 2 will determine the functions of the transcription factors, described in aim 1, in the promoters of prolactin (PRL), PR, and fibronectin (FN) in stromal/decidual. Aim 3 will determine how these transcription factors act on the endogenous gene, IGFBP-1, PRL, PR and FN. Aim 4 will determine the effects of estrogen, progesterone and synthetic steroids, agonists/antagonists on the mRNA levels of the functional transcription factors. Results obtained from the proposed study will help us to understand how the transcription factors control the process of decidualization in the human endometrial stromal/decidual cells. This information can be applied to improving the fertility regulation, tissue-specific fertility control, treatment of implantation failure and pregnancy disorder.