Genomic Fingerprint of PGF2alpha and LH actions on the *

描述（由申请人提供）：黄体（CL）在其有限的寿命期间经历结构和功能的动态变化。然而，尽管循环[促黄体激素] LH缺乏可辨别的降低，但在非生育周期结束时发生的自发性黄体溶解的机制仍缺乏表征。此外，CL的寿命通过绒毛膜促性腺激素（CG）延长的机制仍然是一个谜，绒毛膜促性腺激素（CG）是垂体LH的功能类似物，由胎盘滋养层在可生育的月经周期中精心制作。利用GnRH拮抗剂诱导的黄体溶解模型，我们已经确定了几个新的基因，其表达由LH在猴CL表明，基因的表达响应于LH的CL功能的维护是至关重要的。我们最近已将单次注射GnRH拮抗剂诱导黄体溶解的方法标准化，以进行黄体功能动力学的研究。累积的实验证据表明，起源于卵巢的前列腺素（PG）F2 α可能在高等灵长类动物中起黄体溶解素的作用。偶然的是，我们观察到在月经周期黄体期的某些日子给予外源性PGF 2 α后，猴的黄体功能下降。鉴于这一令人兴奋的发现对阐明自发性黄体溶解机制具有重要意义，我们假设PGF 2 α细胞内信号传导干扰LH作用，从而在非生育周期诱导自发性黄体溶解。为了验证这一假设，将研究以下目标：（1）阐明与PGF 2 α作用相关的信号转导机制;（2）研究PGF 2 α激活途径与LH细胞内信号传导相互作用从而在非生育周期中减少黄体功能的机制。将对猴CL进行全局基因表达谱分析，以鉴定PGF 2 α处理后或LH分泌抑制后的差异表达基因，从而鉴定与黄体溶解相关的信号传导途径。两个系统之间的表达模式将通过各种方法进行研究，以确定与自发性黄体溶解相关的生化途径。

DESCRIPTION (provided by applicant): The corpus luteum (CL) undergoes dynamic changes in structure and function during its finite life-span. However, the mechanism(s) responsible for spontaneous luteolysis that occurs at the end of the non-fertile cycle, despite the lack of a discernible decrease in circulating [luteinizing hormone] LH, remains poorly characterized. Also, the mechanism by which the life-span of the CL gets extended by the chorionic gonadotropin (CG), a functional analog of pituitary LH, elaborated by the placental trophoblast in fertile menstrual cycles remains a mystery. Utilizing the GnRH antagonist induced-luteolysis model, we have identified several novel genes whose expressions were regulated by LH in the monkey CL indicating that expressions of genes in response to LH is critical to the maintenance of CL function. We have recently standardized a single injection of GnRH antagonist to induce luteolysis for carrying out studies on the kinetics of luteal function. Accumulated experimental evidence suggests that prostaglandin (PG)F2alpha originating within the ovary might function as luteolysin in higher primates. Fortuitously, we observed a decreased luteal function following exogenous administration of PGF2alpha on certain days of the luteal phase of the menstrual cycle in monkeys. In view of this exciting finding that has implications on elucidating mechanisms of spontaneous luteolysis, we hypothesize that PGF2alpha intracellular signaling interferes with LH action to induce spontaneous luteolysis during non-fertile cycle. To test this hypothesis, the following objectives will be investigated: (1) to elucidate the mechanisms of signal transduction associated with PGF2alpha action; and (2) to investigate the mechanism by which PGF2alpha-activated pathways cross talk with intracellular signaling of LH to curtail luteal function during the non-fertile cycle. Global gene expression profiling analysis on the monkey CL will be performed to identify differentially expressed genes in response to PGF2alpha treatment or after LH secretion inhibition to identify signaling pathways associated with luteolysis. Expression patterns between the two systems will be investigated by various approaches to identify the biochemical pathways associated with spontaneous luteolysis.