REGULATION OF THE PRIMATE CORPUS LUTEUM

这项研究的长期目标是阐明这种机制。 对终止时黄体退化负责 以及了解非生育月经周期的机制 绒毛膜促性腺激素在早期挽救黄体的作用 怀孕了。在前几年的支持中，我们调查了 垂体促黄体生成素分泌对维持黄体功能的作用 寿命。虽然我们的结果提供了明确的证据证明 分泌物是孕酮产生所必需的。 黄体，我们的数据也证明了自发黄体 在非生育周期终止时的回归不是由于变化 在黄体生成素的分泌模式中。因此，该计划的总体目标是 目前的建议是调查语料库的内在机制 可能与黄体退化有关的黄体。 我们要检验的总体假设是， 黄体(类固醇和蛋白质的合成和释放)是 独立地叠加在细胞计时机制上，从而导致 在组织的高度可重复性的14-16天寿命内。这个 这一假说的基础是我们先前研究的直接结果 在其中，我们演示了三天的LH支持中断 黄体导致黄体孕酮完全停止。 分泌物，但不干扰组织的寿命。 为了验证这一假设，我们将确定黄体是否 退化是由于一种程序性细胞死亡，在这种死亡中 基因组DNA的降解伴随着保真度的损失 转录过程是黄体发育过程中的早期事件 回归。为此，我们将检查基因组的完整性 黄体退化期和稳定期的DNA水平 主要黄体细胞蛋白的mRNAs。我们的假设是 有观察到基因组DNA的降解先于 黄体退化过程中稳态信使核糖核酸水平的降低。 此外，我们还将确定hCG挽救黄体是否 是由于DNA降解的延迟和/或 主要核糖核酸的表达浓度和/或持续时间 黄体细胞蛋白。最后，我们将使用我们的GnRH脉冲动物模型 以确定黄体生成素是否参与到时刻的调节中 黄体中的基因表达，或者促黄体生成素是否仅起作用 调节已有的类固醇生成途径。 这些研究除了提供有关 对黄体的调节，也可能透露出关于黄体的新信息 细胞机制参与肿瘤的病理状态 黄体期不足和黄体期短，两者都是 与人类不孕不育有关。

The long-term objective of this research is to elucidate the mechanisms responsible for the regression of the corpus luteum at the termination of non-fertile menstrual cycles as well as to understand the mechanisms by which chorionic gonadotropin rescues the corpus luteum during early pregnancy. In previous years of support we investigated the role of pituitary LH secretion on the maintenance of luteal function and lifespan. While our results provided unequivocal evidence that LH secretion is absolutely required for progesterone production by the corpus luteum, our data also demonstrated that spontaneous luteal regression at the termination of non-fertile cycles in not due to changes in the pattern of LH secretion. Therefore, the overall goal of the current proposal is to investigate mechanisms intrinsic to the corpus luteum that may be responsible for luteal regression. The overall hypothesis we wil test is that the specialized functions of the corpus luteum (steroid and protein synthesis and release) are independently superimposed on a cellular timing mechanism that results in a highly reproducible 14-16 day lifespan of the tissue. The foundation for this hypothesis is a direct result of our previous studies in which we demonstrated that a three day interruption of LH support to the corpus luteum caused a total cessation of luteal progesterone secretion but did not interfere with the lifespan of the tissue. In pursuit of testing this hypothesis, we will determine if luteal regression is due to a type of programmed cell death in which the degradation of genomic DNA with the concomitant loss in the fidelity of transcriptional processes is an early event in the process of luteal regression. For this purpose, we wil examine the integrity of genomic DNA during the period of luteal regression as well as steady state levels of mRNAs for major luteal cell proteins. Our hypothesis would be supported by the observation that degradation of genomic DNA precedes reductions in steady state mRNA levels during luteal regression. In addition, we will determine if the rescue of the corpus luteum by hCG is due to a delay in the degradation of DNA and/or increases in either the concentration and/or the duration of expression of mRNAs for major luteal cell proteins. Lastly, we will use our GnRH-pulsed animal model to determine whether LH is involved in the moment to moment regulation of gene expression in the corpus luteum or whether LH serves solely to regulate pre-existing pathways for steroidogenesis. These studies, in addition to providing basic information on the regulation of the corpus luteum, may also shed new information on the cellular mechanisms involved in the pathological conditions of the inadequate luteal phase and the short luteal phase, both of which are associated with infertility in humans.