This is a Shannon Award providing partial support for the research projects that fall short of the assigned institute's funding range but are in the margin of excellence. The Shannon Award is intended to provide support to test the feasibility of the approach; develop further tests and refine research techniques; perform secondary analysis of available data sets; or conduct discrete projects that can demonstrate the PI's research capabilities or lend additional weight to an already meritorious application. The abstract below is taken from the original document submitted by the principal investigator. Prostaglandins (PG) have an essential role in regulating ovarian function including key aspects of ovulation, luteinization, and luteal regression. Despite this central role in reproductive physiology the temporal and cellular patterns of expression for the PG receptors, as well as the hormonal regulation of this expression, have not been defined. With the recent cloning of the cDNAs for the various subtypes of PGE and PGF2alpha receptors, an analysis of both the protein and mRNA for these receptors is possible. The research in this study is designed to evaluate the mechanisms involved in expression of the prostaglandin F2alpha and PGE receptors in the preovulatory follicle and corpus luteum. Our working hypotheses for these studies is that the LH surge, or other aspects of the luteinization process, induce the expression of PGF2alpha and PGE2 receptors and PG-responsive intracellular pathways, thus, establishing the cellular mechanisms for ovulation, luteinization, and regression of the corpus luteum.
The Specific Aims are: 1) Characterize the temporal pattern for the in vivo expression of PGF2alpha receptors during late follicular and early luteal development. 2) Determine the role of cAMP-dependent protein kinase and progesterone in the differentiation of PGF2alpha responsiveness in cultured follicular cells. 3) Determine whether small luteal cells can be induced to express PGF2alpha receptors and responsiveness (distinctive property of the large luteal cell phenotype) by forskolin. Determine the role of protein kinase C and free intracellular calcium concentrations in downregulation of the mRNA for the PGF2alpha receptor by homologous ligand. 4) Determine the subtype of PGE receptors expressed in the preovulatory follicle and corpus luteum. Determine the temporal pattern of expression for the PGE receptors during late follicular and early luteal development. An understanding of the regulation of PG receptor expression in the corpus luteum will not only advance our current knowledge of reproductive physiology, but will allow for the rational development of contraceptives or infertility treatments that target prostaglandin action in the ovary.
