As part of the physiological process leading to ovulation, luteinizing hormone causes a rise in prostaglandin levels in preovulatory ovarian follicles. The overall goal of this research is a detailed understanding of the hormonal regulation of prostaglandin synthesis. Our objective is the elucidation of the biochemical events by which luteinizing hormone stimulates this increase in prostaglandin synthase activity in the rat ovary. The experiments are designed to test the possibility of enzyme activation versus production of new enzyme, as well as to probe the events leading to either of these possibilities. The presence of prostaglandin synthase in various ovarian cell types will be detected by immunohistochemistry utilizing a monoclonal antibody to this enzyme developed previously. The changes in the quantity of prostaglandin synthase following gonadotropin stimulation will be assessed by enzyme immunoassay of ovarian extracts. Immunoaffinity chromatography will be employed to purify the enzyme for determination of the endogenous factors which control its activity, and to obtain basic biochemical data on this protein. In addition, hybridization of specific mRNA for prostaglandin synthase in cell extracts or tissue sections may also be performed to assess the regulatory steps for hormonal control. The proposed studies will provide basic insights into the regulation of biochemicals (prostaglandins) essential for mammalian ovulation. Clinical situations exist which exhibit unruptured large follicles similar to those resulting from lack of prostaglandins in experimental animals. Extrapolation of the anticipated results, therefore, to clinical practice is possible although distant. The proposed research may have implications beyond ovulation, since prostaglandins have been implicated in the processes of LH release, luteolysis, parturition, etc. and in diseases such as cancer, atherosclerosis, and diabetes.
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