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.
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| Singh, Padmasana; Krishna, Amitabh; Sridaran, Rajagopala et al. (2011) Immunohistochemical localization of GnRH and RFamide-related peptide-3 in the ovaries of mice during the estrous cycle. J Mol Histol 42:371-81 |
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