REGULATION OF THE PRIMATE CORPUS LUTEUM

本研究的长期目标是阐明 负责终止时黄体的退化 以及了解非生育月经周期的机制 绒毛膜促性腺激素通过其在早期 怀孕 在过去几年的支持中，我们调查了 垂体LH分泌对黄体功能的维持和 寿命 虽然我们的研究结果提供了明确的证据， 分泌是绝对必要的孕酮生产的 黄体，我们的数据还表明，自发黄体， 非生育周期终止时的退化不是由于变化 LH分泌的模式。 因此， 目前的建议是调查机制的语料库内在 可能导致黄体退化。 我们要检验的总体假设是， 黄体（类固醇和蛋白质合成和释放） 独立地叠加在细胞计时机制上， 在组织的14-16天寿命中高度可再现。 的 这一假设的基础是我们先前研究的直接结果 我们证明了三天的LH支持中断， 黄体引起黄体孕酮的完全停止 分泌，但不干扰组织的寿命。 为了验证这一假设，我们将确定黄体功能是否 退化是由于一种类型的程序性细胞死亡， 基因组DNA的降解伴随着 转录过程是黄体过程中的早期事件 回归分析 为此，我们将检查基因组的完整性， 黄体退化期间的DNA以及稳态水平 主要黄体细胞蛋白的mRNA。 我们的假设是 这得到了基因组DNA降解先于 黄体退化期间稳态mRNA水平的降低。 此外，我们还将确定hCG是否能挽救黄体， 是由于DNA降解的延迟和/或 主要肿瘤的mRNA表达的浓度和/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LH是否参与瞬间调节 黄体中基因表达或LH是否仅用于 调节类固醇生成的预先存在的途径。 这些研究除了提供关于 调节黄体，也可能揭示新的信息， 细胞机制参与的病理条件下， 黄体期不足和黄体期短，两者都是 与人类不育症有关。

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.