Regulation of Prostaglandins in Periovulatory Follicles

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DESCRIPTION (provided by applicant): The LH/FSH surge sets in motion a cascade of events that culminates in the remarkable rupture of the follicular wall at the apex and the subsequent release of the oocyte-cumulus complex. Despite its critical importance to reproduction and fertility, and despite decades of research, there are many gaps in our knowledge of the regulation of the ovulatory process. Many regulators and pathways have been hypothesized to be involved in mammalian ovulation, but results of previous studies have highlighted essential roles for progesterone and prostaglandins (PGs). Cattle provide an ideal animal model for studying the complex events of the periovulatory period. We have validated a model for inducing periovulatory follicular development in cattle and we now propose to use it to test hypotheses about these two key regulators of ovulation and their receptors. In Specific Aims 1 and 2, the timing, cellular site(s) of synthesis, biosynthetic pathway, and hormonal regulation of the periovulatory increase in PG synthesis will be examined. The hypothesis to be tested is that both theca and granulosa cells respond to the preovulatory LH/FSH surge with an increase in PG production, mediated by the surge-induced rise in progesterone, which in turn induces PGF2a synthesis, via reduction from PGE2. In Specific Aim 3 we will test the hypothesis that the effects of progesterone on prostaglandin production by the periovulatory follicle are at least partially mediated through progesterone-induced increases in oxytocin. Although PGs are essential for ovulation, virtually nothing is known about the expression of PG receptors during the periovulatory period. In Specific Aim 4, the temporal expression of mRNA for PGF2alpha receptor in bovine periovulatory follicles will be determined. The hypothesis that mRNA for the receptor is expressed coordinately with the rise in PG synthesis and, is localized to the theca cells of the periovulatory follicle will be tested. Specific Aim 5 is designed to test the hypothesis that the LWFSH surge induces progesterone receptor (PR) in follicular cells of the periovulatory follicle and that these receptors mediate progesterone's effects on PG production. Together these experiments will provide new knowledge about the regulation of, and relationship between, these two essential mediators of ovulation and their receptors.