MOLECULAR REGULATION OF LUTEAL FUNCTION

黄体功能的分子调节

基本信息

批准号：
2765563
负责人：
GEULA GIBORI
金额：
$ 3.87万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-03-01 至 2002-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2765563
关键词：
corpus luteum gene expression genetic promoter element granulosa cell hormone regulation /control mechanism hydroxysteroid dehydrogenases immunoprecipitation interleukin 6 laboratory rat nuclear factor kappa beta nucleic acid probes progesterone progesterone receptors prolactin protein structure function receptor expression tissue /cell culture transcription factor

项目摘要

The production of progesterone by the corpus luteum is crucial to prepare the endometrium for implantation and for the maintenance of pregnancy. Recent investigations have revealed that progesterone can acts also in luteal cells to sustain its own production through an intracrine mechanism, despite the lack of progesterone receptor in the rat corpus luteum. Signaling occurs through the glucocorticoid receptor. The lack of progesterone receptor is puzzling since the expression of this gene is increased by estradiol, and since the rat corpus luteum produces estradiol, expresses estrogen receptors, and is highly responsive to estradiol. Studies performed in both laboratories involved in the proposed study, have demonstrated that progesterone sustains its own production by preventing the expression of at least two gene products: 20alpha-hydroxysteroid dehydrogenase, an enzyme which catabolizes progesterone; and interleukin-6, a cytokine detrimental for steroidogenesis. The overall aims of this proposal are: 1) to determine the reason by which the progesterone receptor is silenced in the rat corpus luteum; 2) to examine the molecular mechanisms whereby progesterone down regulates the expression of luteal 20alpha- hydroxysteroid dehydrogenase; and 3) to determine whether the inhibition of interleukin-6 expression by progesterone in the corpus luteum involves the nuclear factor kappa-B (NF-kappaB) family of transcription factors.

叶酸肠菌的产生孕酮对于为子宫内膜植入和维持妊娠而产生至关重要。最近的调查表明，尽管大鼠体体中缺乏孕激素受体，但孕酮也可以在黄体细胞中作用于黄体细胞来维持其自身的产生。信号通过糖皮质激素受体发生。由于雌二醇增加了该基因的表达，因此缺乏孕激素受体令人困惑，并且由于大鼠叶黄素会产生雌二醇，表达雌激素受体，并且对雌二醇的反应很高。在参与拟议研究的两个实验室进行的研究都表明，孕酮通过防止至少两种基因产物的表达来维持其自身的产生：20α-羟基甾体脱氢酶，一种酶，可分解孕酮的酶；和白介素-6，一种细胞因子对类固醇生成有害。该提案的总体目的是：1）确定大鼠叶黄素中孕酮受体沉默的原因； 2）检查分子机制，从而调节孕酮调节黄体20α-羟基固醇脱氢酶的表达； 3）确定孕酮在黄体中对白介素-6表达的抑制是否涉及转录因子的核因子kappa-b（NF-kappab）家族。