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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
3R01HD022299-04S1
Application #
3321817
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1986-02-01
Project End
1990-03-31
Budget Start
1989-08-01
Budget End
1990-03-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Curry Jr, T E; Bryant, C; Clark, M R (1991) Cellular localization of ovarian prostaglandin endoperoxide synthase during pseudopregnancy in the rat. Biol Reprod 44:897-905
Curry Jr, T E; Bryant, C; Haddix, A C et al. (1990) Ovarian prostaglandin endoperoxide synthase: cellular localization during the rat estrous cycle. Biol Reprod 42:307-16
Van Voorhis, B J; Huettner, P C; Clark, M R et al. (1990) Immunohistochemical localization of prostaglandin H synthase in the female reproductive tract and endometriosis. Am J Obstet Gynecol 163:57-62
Kauma, S W; Curry Jr, T E; Powell, D E et al. (1990) Localization of prostaglandin endoperoxide synthase in the human corpus luteum. Hum Reprod 5:800-4
Marshburn, P B; Shabanowitz, R B; Clark, M R (1990) Immunohistochemical localization of prostaglandin H synthase in the embryo and uterus of the mouse from ovulation through implantation. Mol Reprod Dev 25:309-16
Price, T M; Kauma, S W; Curry Jr, T E et al. (1989) Immunohistochemical localization of prostaglandin endoperoxide synthase in human fetal membranes and decidua. Biol Reprod 41:701-5
Marshburn, P B; Clark, M R; Shabanowitz, R B (1989) Immunohistochemical localization of prostaglandin H synthase in the epididymis and vas deferens of the mouse. Biol Reprod 41:491-7
Clark, M R; Hummel, W P; Eyster, K M (1989) Suppression of LH-stimulated prostaglandin and progesterone accumulation in rat granulosa cells by isoquinolinesulfonamide protein kinase inhibitors. Steroids 54:563-74
Parr, M B; Parr, E L; Munaretto, K et al. (1988) Immunohistochemical localization of prostaglandin synthase in the rat uterus and embryo during the peri-implantation period. Biol Reprod 38:333-43
Curry Jr, T E; Malik, A; Clark, M R (1987) Ovarian prostaglandin synthase: immunohistochemical localization in the rat. Am J Obstet Gynecol 157:537-43

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