Prostaglandin-independent anovulatory mechanism of indomethacin action: inhibition of tumor necrosis factor alpha-induced sheep ovarian cell apoptosis.
Prostaglandin-independent anovulatory mechanism of indomethacin action: inhibition of tumor necrosis factor alpha-induced sheep ovarian cell apoptosis.
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吲哚美辛作用的前列腺素非依赖性无排卵机制:抑制肿瘤坏死因子α诱导的绵羊卵巢细胞凋亡。
作者:
W. Murdoch;S. A. Lund
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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影响因子:
--
作者:
ABRAMSON, SB;WEISSMANN, G
通讯作者:
WEISSMANN, G
影响因子:
4.8
作者:
L. Espey;C. Norris;D. Saphire
通讯作者:
L. Espey;C. Norris;D. Saphire
影响因子:
7.7
作者:
Ruan, H;Miles, PDG;Lodish, HF
通讯作者:
Lodish, HF
DOI:
10.1016/0090-6980(88)90063-9
发表时间:
1988
期刊:
Prostaglandins
影响因子:
--
作者:
Espey,LL;Kohda,H;Mori,T;Okamura,H
通讯作者:
Okamura,H