Ibuprofen modulation of human chorionic gonadotropin-induced ornithine decarboxylase activity and ovulation in the rabbit ovary.
The activity of ornithine decarboxylase, the rate-limiting enzyme in polyamine synthesis, increases as granulosa cells proliferate in developing follicles. Both luteinizing hormone and prostaglandins stimulate ornithine decarboxylase activity. Here, we sought to determine the relative contributions of both trophic stimuli to ornithine decarboxylase activity in the preovulatory rabbit ovary. Baseline ovarian ornithine decarboxylase activity, determined by measuring the release of CO2 from (1-14C)-ornithine, was 13.4 +/- 1.27 (mean +/- SD) pmol of carbon dioxide per hour per milligram of protein. Treatment with ibuprofen, a prostaglandin synthetase inhibitor, led to a significant (p less than 0.05) decrease in the baseline ovarian ornithine decarboxylase activity (4.7 +/- 0.29 pmol of carbon dioxide per hour per milligram of protein). Administration of human chorionic gonadotropin (hCG) (50 IU/kg intramuscularly) to adult rabbits (2.5 to 3.5 kg) elicited a 1,200% elevation of ovarian ornithine decarboxylase activity 5 hours after injection; there was a return to baseline by 11 hours after injection. Stimulation with human chorionic gonadotropin led to ovulation in 22.2%, 25%, and 60% of rabbits at 7, 9, and 11 hours after treatment, respectively. Single-dose ibuprofen treatment (5 mg/kg intramuscularly), 7 hours after human chorionic gonadotropin administration inhibited ovulation and elevated ovarian ornithine decarboxylase activity. These results indicate that ibuprofen effectively inhibits ovulation in hCG-stimulated rabbit ovaries in the presence of a significant (p less than 0.001) elevation in ovarian ornithine decarboxylase activity. Thus, different intracellular mechanisms are involved in the prostaglandin modulation of basal and hCG-stimulated cells during the course of preovulatory follicle maturation.
D000818:Animals; D006063:Chorionic Gonadotropin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005260:Female; D007052:Ibuprofen / Q000494:pharmacology*; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010053:Ovary / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D010060:Ovulation / Q000187:drug effects*
D006063:Chorionic Gonadotropin; D009955:Ornithine Decarboxylase; D007052:Ibuprofen