Priyanka S, Jayaram P, Sridaran R, Medhamurthy R
Department of Molecular Reproduction, Indian Institute of Science, Bangalore, India.
Endocrinology. 2009 Mar;150(3):1473-84. doi: 10.1210/en.2008-0840. Epub 2008 Nov 6.
Although LH is essential for survival and function of the corpus luteum (CL) in higher primates, luteolysis occurs during nonfertile cycles without a discernible decrease in circulating LH levels. Using genome-wide expression analysis, several experiments were performed to examine the processes of luteolysis and rescue of luteal function in monkeys. Induced luteolysis with GnRH receptor antagonist (Cetrorelix) resulted in differential regulation of 3949 genes, whereas replacement with exogenous LH (Cetrorelix plus LH) led to regulation of 4434 genes (1563 down-regulation and 2871 up-regulation). A model system for prostaglandin (PG) F(2alpha)-induced luteolysis in the monkey was standardized and demonstrated that PGF(2alpha) regulated expression of 2290 genes in the CL. Analysis of the LH-regulated luteal transcriptome revealed that 120 genes were regulated in an antagonistic fashion by PGF(2alpha). Based on the microarray data, 25 genes were selected for validation by real-time RT-PCR analysis, and expression of these genes was also examined in the CL throughout the luteal phase and from monkeys treated with human chorionic gonadotropin (hCG) to mimic early pregnancy. The results indicated changes in expression of genes favorable to PGF(2alpha) action during the late to very late luteal phase, and expressions of many of these genes were regulated in an opposite manner by exogenous hCG treatment. Collectively, the findings suggest that curtailment of expression of downstream LH-target genes possibly through PGF(2alpha) action on the CL is among the mechanisms underlying cross talk between the luteotropic and luteolytic signaling pathways that result in the cessation of luteal function, but hCG is likely to abrogate the PGF(2alpha)-responsive gene expression changes resulting in luteal rescue crucial for the maintenance of early pregnancy.
尽管促黄体生成素（LH）对于高等灵长类动物黄体（CL）的存活和功能至关重要，但在未受孕周期中黄体溶解仍会发生，而循环中的LH水平却没有明显下降。利用全基因组表达分析，进行了多项实验来研究猴子黄体溶解和黄体功能挽救的过程。用促性腺激素释放激素（GnRH）受体拮抗剂（西曲瑞克）诱导黄体溶解导致3949个基因的差异调节，而用外源性LH替代（西曲瑞克加LH）则导致4434个基因的调节（1563个下调和2871个上调）。建立了猴子中前列腺素（PG）F2α诱导黄体溶解的模型系统，并证明PGF2α调节了CL中2290个基因的表达。对LH调节的黄体转录组分析表明，有120个基因受到PGF2α的拮抗调节。基于微阵列数据，选择了25个基因通过实时逆转录聚合酶链反应（RT-PCR）分析进行验证，并且还在整个黄体期以及用人类绒毛膜促性腺激素（hCG）处理以模拟早期妊娠的猴子的CL中检测了这些基因的表达。结果表明，在黄体晚期至极晚期有利于PGF2α作用的基因表达发生了变化，并且这些基因中的许多基因的表达在外源性hCG处理下以相反的方式受到调节。总体而言，这些发现表明，可能通过PGF2α对CL的作用来减少下游LH靶基因的表达，是导致黄体功能停止的促黄体生成素和溶黄体信号通路之间相互作用的机制之一，但hCG可能会消除PGF2α反应性基因表达的变化，从而导致对维持早期妊娠至关重要的黄体挽救。
