ENDOMETRIUM GENE REGULATION DURING DECIDUALIZATION

子宫内膜蜕化过程中的基因调控

• 批准号: 6499068
• 负责人: LINDA TSENG
• 金额: $ 27.54万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6499068
• 关键词: binding proteins; cell differentiation; decidua; developmental genetics; endometrium; estrogens; fibronectins; gene induction /repression; genetic promoter element; hormone regulation /control mechanism; human genetic material tag; human tissue; insulinlike growth factor; menstrual cycle; nucleic acid sequence; postpartum; pregnancy; progesterone receptors; progestins; prolactin; transcription factor

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.

这项研究的长期目标是确定