ENDOMETRIUM GENE REGULATION DURING DECIDUALIZATION

本研究的长期目标是确定 在子宫内膜细胞蜕膜化过程中表达的转录因子。 我们假设，少数转录因子调控着细胞的增殖。 下游靶基因激活，以形成蜕膜瘤， 胚胎发育和维持多种生物功能， 怀孕 为了进行这项研究，人类子宫内膜细胞培养 它概括了体内蜕膜化的过程， 确立了习 使用这个系统，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。 我们还确定 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的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： 目的1将确定和表征转录因子， 调节IGFBP-1基因的激活。 该项研究将集中 C/TCAAT、CRE、Sp1和 加塔基序和PRE基序的孕酮受体（PR）。 目标2将 确定转录因子的功能，如目的所述 1，在催乳素（PRL），PR和纤连蛋白（FN）的启动子中， 基质/蜕膜。 Aim 3将确定这些转录因子 作用于内源基因IGFBP-1、PRL、PR和FN。 目标4将 确定雌激素、孕激素和合成类固醇的作用， 激动剂/拮抗剂对功能性转录的mRNA水平的影响 因素 从拟议研究中获得的结果将有助于我们 了解转录因子如何控制 人子宫内膜间质/蜕膜细胞的蜕膜化。 这 信息可用于改善生育率调节， 组织特异性生育控制、植入失败的治疗以及 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.