PROGESTIN AND RELAXIN EFFECTS ON ENDOMETRIAL PROLACTIN

孕激素和松弛素对子宫内膜催乳素的影响

• 批准号: 3316475
• 负责人: LINDA TSENG
• 金额: $ 12.28万
• 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 1992-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3316475
• 关键词: DNA replication; calcium; cell differentiation; cell growth regulation; cell transformation; cyclic AMP; endometrium; female; fertilization; gene expression; genetic transcription; hormone biosynthesis; hormone regulation /control mechanism; human tissue; messenger RNA; monoclonal antibody; progestins; prolactin; radioassay; relaxin; second messengers; stromal cells; tissue /cell culture

Recent studies show that progestin and relaxin synergistically induce the production of prolactin (PRL) and other cellular proteins in human endometrial stromal cells. The concerted effects of progestin and relaxin on the induction of prolactin are closely associated with the growth and decidualization of the endometrial stromal cells at the time of conception and during pregnancy. The long term goal of this project is to investigate the role of individual hormones on the induction of PRL at different stages of the development of endometrial stromal cells. The project proposes to investigate the mechanism of action of progestin and relaxin on the various levels of PRL gene expression and the development of human endometrial stromal cells in a long-term culture system. (1) The rate of PRL synthesis, steady-state levels of PRLmRNA, the rate of degradation of PRLmRNA, and the rate of transcription of PRLmRNA, will be investigated at the initial phase and during the continuing PRL production period. (2) The development of endometrial stromal cells under the influence of progestin and relaxin in vitro will be studied by comparing the induction pattern of PRL in the stromal cells to that in the decidua, a fully differentiated endometrium; and by investigating DNA synthesis, total DNA and protein contents. (3) The second messenger(s) of relaxin and the transmembrane signal pathways which transmit the signal of relaxin to activate the PRL gene expression will be investigated in progestin-primed endometrial stromal cells and in decidual cells. This project provides a system to study the PRL gene expression during the differentiation of the endometrium, a biological system uniquely different from the pituitary system. This proposal will demonstrate the transformation of a hormone target tissue (the endometrium) into an autocrine system (the decidua). Understanding the role of relaxin and endogenous hormone on decidualization will improve the successful rate of implantation. It will also offer new pharmacological avenues to fertility regulation and the development of new contraceptive agents, the prevention and treatment of reproductive dysfunction and neoplastic transformation of the endometrium.

最近的研究表明，槲皮素和松弛素协同诱导， 人催乳素（PRL）和其他细胞蛋白质的产生 子宫内膜间质细胞。 槲皮素和松弛素的协同作用 催乳素的诱导与生长密切相关， 受孕时子宫内膜间质细胞的脱落 和怀孕期间。 该项目的长期目标是调查 不同时期激素对催乳素诱导的作用 子宫内膜间质细胞的发育。 本项目拟研究槲皮素的作用机制 和松弛素对PRL基因表达水平的影响， 人子宫内膜间质细胞的长期培养 系统 (1)PRL合成速率、PRL mRNA稳态水平、 PRLmRNA的降解速率和PRLmRNA的转录速率， 将在初始阶段和持续PRL期间进行调查 生产期。 (2)子宫内膜间质细胞在体外发育的实验研究 将通过以下方法研究在体外的白藜芦醇蛋白和松弛素的影响： 比较基质细胞中PRL的诱导模式与基质细胞中PRL的诱导模式， 蜕膜，完全分化的子宫内膜;通过研究DNA 合成、总DNA和蛋白质含量。 (3)第二个使者， 松弛素和跨膜信号传导途径， 松弛素激活PRL基因表达将在 孕激素致敏的子宫内膜间质细胞和蜕膜细胞。 本项目提供了一个系统，研究PRL基因表达过程中， 子宫内膜的分化，一个独特的生物系统， 从垂体系统。 该提案将展示 将激素靶组织（子宫内膜）转化为 自分泌系统（蜕膜）。 了解松弛素的作用， 内源性激素对蜕膜化的影响可提高 置入 它还将为生育提供新的药理学途径 管制和开发新的避孕药， 生殖功能障碍和肿瘤转化的治疗 子宫内膜