Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0277787 (stigma)
 13,352 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indomethacin, a nonsteroidal anti-inflammatory agent, is a potent inhibitor of ovulation in vertebrates. The presumptive obligate anovulatory mode of indomethacin action is via suppression of ovarian prostaglandin production. We report that a very high systemic dose of indomethacin (800 mg i.m.) is required to block ovulation in gonadotropin-treated anestrous ewes. A lower dose of indomethacin (200 mg), which negated the preovulatory rise in follicular prostaglandin (PGF(2alpha)) biosynthesis, did not prevent ovulation. Endothelial secretion of tumor necrosis factor (TNF)-alpha within the apical follicular wall (prospective site of rupture) was not altered by indomethacin; notwithstanding, the apoptosis (DNA-fragmentation)-inducing effect of TNF-alpha (a determinant of ovulatory stigma formation) was attenuated by 800 (but not 200) mg indomethacin. A suprapharmacological concentration of indomethacin also was necessary to protect ovarian surface epithelial cells from a (prostaglandin-independent) cytotoxic effect of TNF-alpha in vitro. It is concluded that indomethacin inhibits ovulation by anti-apoptotic mechanisms that can be dissociated from the paradigm of prostanoid down-regulation.
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PMID:Prostaglandin-independent anovulatory mechanism of indomethacin action: inhibition of tumor necrosis factor alpha-induced sheep ovarian cell apoptosis. 1057 16

Tissue dissolution and remodelling are associated with the processes of rupture of the ovulatory follicle and formation of the corpus luteum. Matrix metalloproteinase 2 (MMP-2) belongs to a family of endopeptidases that cleave extracellular proteins; its primary substrate is the lattice network of basement membranes that support epithelial cells and endothelium. The aim of this study was to ascertain a putative regulatory role of MMP-2 relevant to the folliculo-luteal transformation in ewes. Luteal regression and the preovulatory surge of gonadotrophins were synchronized by administration of PGF(2alpha) and GnRH on days 14.0 and 15.5 of the oestrous cycle, respectively. Dominant antral follicles present during pro-oestrus consistently ovulate approximately 24 h after GnRH administration. Normal IgG or a bioactivity-neutralizing MMP-2 monoclonal antibody was injected into the antral cavity of preovulatory follicles at 8 h after GnRH administration. Jugular blood samples were obtained for serum progesterone analysis and ovaries were removed for light microscopic morphometry on day 8. A definitive ovulation stigma was evident in control ewes. The antra of ruptured follicles had largely been supplanted with luteal tissue. In contrast, the ovarian surface contiguous with follicles injected with anti-MMP-2 was smooth and undisturbed, which is indicative of a failure of ovulation. Luteinized unruptured follicles were filled with (entrapped) fluid. Corpora lutea of control animals contained numerous connective tissue projections that provided a framework for cellular migration and angiogenesis. Luteal tissues that surrounded the cavity of antibody-treated follicles lacked trabeculae and were deficient in blood vessels. Systemic venous progesterone concentrations were lower in ewes with a luteinized unruptured follicle compared with those with a corpus luteum. It is proposed that MMP-2 is a mediator of ovulation and luteal development.
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PMID:Role of matrix metalloproteinase 2 in the ovulatory folliculo-luteal transition of ewes. 1220 8