MOLECULAR REGULATION OF LUTEAL FUNCTION

黄体产生的黄体酮对于准备着床的子宫内膜和维持妊娠至关重要。最近的研究表明，尽管大鼠黄体缺乏黄体酮受体，黄体酮也可以在黄体细胞中通过分泌机制维持自身的生产。信号通过糖皮质激素受体发生。黄体酮受体的缺失令人费解，因为雌二醇增加了该基因的表达，而大鼠黄体产生雌二醇，表达雌激素受体，对雌二醇反应强烈。在两个实验室进行的研究表明，黄体酮通过阻止至少两种基因产物的表达来维持自身的生产：20 α -羟基类固醇脱氢酶，一种分解黄体酮的酶；白细胞介素-6，一种对类固醇生成有害的细胞因子。本研究的总体目标是：1)确定大鼠黄体中黄体酮受体沉默的原因；2)探讨黄体酮下调黄体20 α -羟类固醇脱氢酶表达的分子机制；3)确定黄体中黄体酮对白细胞介素-6表达的抑制是否涉及核因子κ b （nf - κ b）家族转录因子。

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.