Dose-dependent effects of indomethacin on ovulation in the sheep: relationship to follicular prostaglandin production, steroidogenesis, collagenolysis, and leukocyte chemotaxis.
A few recent investigations have indicated that it is possible for mammalian ovulation to progress to completion in the absence of a preovulatory rise in ovarian prostanoid production and that the antiovulatory mode of action of antiinflammatory agents (e.g., indomethacin) could be independent of their ability to inhibit the cyclooxygenase pathway of arachidonate metabolism. Mature ewes were treated during the preovulatory period with a systemic dosage of indomethacin that either consistently did (500 mg) or did not (100 mg) prevent follicular rupture. With both dosages, the rise in follicular production of prostaglandin F2 alpha following the surge in secretion of LH was negated. Indomethacin did not affect periovulatory patterns of change in follicular tissue concentrations of estradiol-17 beta, testosterone, or progesterone. The 500-mg dose of indomethacin inhibited collagen breakdown within the follicular wall as deduced from measurement of tissue levels of hydroxyproline. In vitro secretion of a follicular leukotactic agent and accumulation of extravascular white blood cells within the theca interna of periovulatory follicles were also suppressed by the ovulation-inhibiting dose of indomethacin. It appears that the blockage of ovulation induced by indomethacin in the sheep is largely unrelated to its capacity to suppress follicular prostaglandin biosynthesis; rather, it is more directly associated with effects on follicular collagenolysis and leukocyte chemoattraction.
Murdoch
W J
WJ
Department of Animal Science, University of Wyoming, Laramie 82071.
McCormick
R J
RJ
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D015237:Dinoprost / Q000096:biosynthesis; D004958:Estradiol / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D006909:Hydroxyproline / Q000378:metabolism; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007958:Leukocyte Count; D007986:Luteinizing Hormone / Q000378:metabolism; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism; D010060:Ovulation / Q000187:drug effects*; D012756:Sheep / Q000502:physiology*; D013256:Steroids / Q000096:biosynthesis
D013256:Steroids; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; D003094:Collagen; D015237:Dinoprost; D006909:Hydroxyproline; D007213:Indomethacin