Harris T G, Battaglia D F, Brown M E, Brown M B, Carlson N E, Viguié C, Williams C Y, Karsch F J
Department of Physiology, University of Michigan, Ann Arbor 48109-0404, USA.
Endocrinology. 2000 Mar;141(3):1050-8. doi: 10.1210/endo.141.3.7393.
Five experiments were conducted to test the hypothesis that PGs mediate the endotoxin-induced inhibition of pulsatile GnRH and LH secretion in the ewe. Our approach was to test whether the PG synthesis inhibitor, flurbiprofen, could reverse the inhibitory effects of endotoxin on pulsatile LH and GnRH secretion in ovariectomized ewes. Exp 1-4 were cross-over experiments in which ewes received either flurbiprofen or vehicle 2 weeks apart. Jugular blood samples were taken for LH analysis throughout a 9-h experimental period. Depending on the specific purpose of the experiment, flurbiprofen or vehicle was administered after 3.5 h, followed by endotoxin, vehicle, or ovarian steroids (estradiol plus progesterone) at 4 h. In Exp 1, flurbiprofen reversed the endotoxin-induced suppression of mean serum LH concentrations and the elevation of body temperature. In Exp 2, flurbiprofen prevented the endotoxin-induced inhibition of pulsatile LH secretion and stimulation of fever, reduced the stimulation of plasma cortisol and progesterone, but did not affect the rise in circulating tumor necrosis factor-alpha. In Exp 3, flurbiprofen in the absence of endotoxin had no effect on pulsatile LH secretion. In Exp 4, flurbiprofen failed to prevent suppression of pulsatile LH secretion induced by luteal phase levels of the ovarian steroids progesterone and estradiol, which produce a nonimmune suppression of gonadotropin secretion. In Exp 5, flurbiprofen prevented the endotoxin-induced inhibition of pulsatile GnRH release into pituitary portal blood. Our finding that this PG synthesis inhibitor reverses the inhibitory effect of endotoxin leads to the conclusion that PGs mediate the suppressive effects of this immune/inflammatory challenge on pulsatile GnRH and LH secretion.
前列腺素（PGs）介导内毒素对母羊脉冲式促性腺激素释放激素（GnRH）和促黄体生成素（LH）分泌的抑制作用。我们的方法是测试PG合成抑制剂氟比洛芬是否能逆转内毒素对去卵巢母羊脉冲式LH和GnRH分泌的抑制作用。实验1 - 4为交叉实验，母羊每隔2周接受氟比洛芬或赋形剂。在9小时的实验期内，采集颈静脉血样进行LH分析。根据实验的具体目的，在3.5小时后给予氟比洛芬或赋形剂，然后在4小时给予内毒素、赋形剂或卵巢类固醇（雌二醇加孕酮）。在实验1中，氟比洛芬逆转了内毒素诱导的平均血清LH浓度抑制和体温升高。在实验2中，氟比洛芬阻止了内毒素诱导的脉冲式LH分泌抑制和发热刺激，降低了血浆皮质醇和孕酮的刺激，但不影响循环肿瘤坏死因子-α的升高。在实验3中，无内毒素时氟比洛芬对脉冲式LH分泌无影响。在实验4中，氟比洛芬未能阻止由卵巢类固醇孕酮和雌二醇的黄体期水平诱导的脉冲式LH分泌抑制，这两种类固醇会产生非免疫性促性腺激素分泌抑制。在实验5中，氟比洛芬阻止了内毒素诱导的脉冲式GnRH释放到垂体门脉血中的抑制作用。我们发现这种PG合成抑制剂能逆转内毒素的抑制作用，由此得出结论：PGs介导了这种免疫/炎症刺激对脉冲式GnRH和LH分泌的抑制作用。
