Abstract
We tested the hypothesis that indomethacin, a potent inhibitor of prostaglandin synthesis, would modify estradiol's effects on tonic and surge concentrations of LH in chronically ovariectomized ewes during the anestrous season. Ewes (n=21) were assigned randomly to one of four treatments: Vehicle+Blank (n=5); Indomethacin+Blank (n=6); Vehicle+Estradiol (n=5); or Indomethacin+Estradiol (n=5). On d=0 (hr=0), ewes began to receive i.m. injections of either indomethacin (4 mg/kg body weight) or corn oil every 8 hr for 9 d. Blood samples were collected every 12 min for 6 hr beginning at −6 hr, +18 hr, and on day 8 (relative to initial injections of indomethacin or vehicle) to assess tonic patterns of secretion of LH. At +24 hr, ewes received blank- or estradiol-containing Silastic implants and were bled hourly for 48 hr. On day 9, ewes received 50 μg of GnRH i.v. and were bled hourly for 8 hr. Serum samples were assayed for LH. Indomethacin had no effect on the following parameters of LH secretion: 1) mean concentrations (ng/ml; 8.4 ± .7 vs 8.9 ± .8; P>.1), 2) pulse frequency/6 hr (4.5 ± .4 vs 4.1 ± .4; P>.1) or 3) pulse amplitude (ng/ml; 15.3 ± 1.1 vs 14.9 ± 1.2; P>.1). Estradiol elicited a surge of LH which began 18.9 ± 1.7 hr after implant insertion, reached a mean peak concentration of 95.3 ± 20.1 ng/ml, and did not differ with respect to indomethacin treatment (P>.1). After the initial estradiol-induced surge of LH, mean concentrations of LH decreased (Vehicle+Blank vs Vehicle+Estradiol: 8.4 ± .7 vs 1.7 ± .7 ng/ml; P<.02), and no pulses of LH were observed. Indomethacin did not modify the ability of estradiol to inhibit secretion of LH (P>.1). Estradiol-treated ewes responded to GnRH with a two-fold greater increase in LH than untreated ewes (463.5 ± 58.3 vs 226.3 ± 61.1 ng/ml; P<.03). In conclusion, indomethacin did not modify the negative or positive feedback effects of estradiol on the secretion of LH in ovariectomized ewes. These data do not support an involvement of prostaglandins in controlling secretion of LH in sheep.
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