Unno N, Wu W X, Wong C H, Bennett P R, Shinozuka N, Nathanielsz P W
Department of Physiology, New York State College of Veterinary Medicine, Cornell University, Ithaca 14853-6401, USA.
Biol Reprod. 1998 Feb;58(2):514-9. doi: 10.1095/biolreprod58.2.514.
It is widely recognized that prostaglandins (PGs) are involved in regulation of the hypothalamo-pituitary-adrenal axis and that the activation of the fetal hypothalamo-pituitary-adrenal axis plays a central role in the process of labor in sheep. However, effects of inhibition of PG synthesis on the maternal and fetal hypothalamo-pituitary-adrenal axis during parturition have not been characterized. We examined the effect of inhibiting PG synthesis on the maternal and fetal hypothalamo-pituitary-adrenal axes during spontaneous term labor by using nimesulide, a PGH synthase (PGHS) inhibitor. Under halothane anesthesia, eight pregnant ewes were instrumented with vascular catheters and myometrial electromyogram (EMG) electrodes at 127 +/- 3 (mean +/- SEM) days gestation (dGA). After onset of labor as evaluated by EMG, nimesulide was infused to four ewes i.v. (30-mg bolus, followed by 6-h infusion at 30 mg/h). Vehicle was infused to the remaining four ewes (controls, CONT). Maternal blood and fetal blood were sampled at 1-h intervals before and during infusion to determine plasma PGE2, ACTH, and cortisol concentrations. Spontaneous labor occurred at 148 +/- 0 dGA in nimesulide-treated ewes and at 144 +/- 1 dGA in CONT ewes. We infused nimesulide from 9 +/- 2 h and vehicle from 8 +/- 2 h after the onset of labor. Maternal and fetal blood gases and pH remained unchanged in all animals. No significant changes were observed in any plasma hormone concentrations measured in CONT ewes and fetuses before and during vehicle infusion. In nimesulide-treated ewes, maternal plasma PGE2 and ACTH concentrations remained unchanged, while maternal plasma cortisol decreased significantly, recovering to baseline by 3 h. In fetuses of nimesulide-treated ewes, plasma PGE2 and ACTH levels showed significant sustained decreases after nimesulide infusion. Fetal plasma cortisol decreased significantly and returned to baseline by 5 h. These results suggest that 1) PG synthesis inhibition by nimesulide has differential effects on the ovine maternal and fetal hypothalamo-pituitary-adrenal axes during spontaneous labor, and 2) PG production plays a physiologic role in regulation of the ovine fetal hypothalamo-pituitary-adrenal axis.
人们普遍认为，前列腺素（PGs）参与下丘脑 - 垂体 - 肾上腺轴的调节，并且胎儿下丘脑 - 垂体 - 肾上腺轴的激活在绵羊分娩过程中起核心作用。然而，分娩期间抑制PG合成对母体和胎儿下丘脑 - 垂体 - 肾上腺轴的影响尚未明确。我们使用PGH合酶（PGHS）抑制剂尼美舒利，研究了在足月自然分娩期间抑制PG合成对母体和胎儿下丘脑 - 垂体 - 肾上腺轴的影响。在氟烷麻醉下，于妊娠127±3（平均±标准误）天（dGA）时，给8只怀孕母羊植入血管导管和子宫肌层肌电图（EMG）电极。通过EMG评估分娩开始后，给4只母羊静脉输注尼美舒利（30 mg推注，随后以30 mg/h输注6小时）。给其余4只母羊输注溶媒（对照组，CONT）。在输注前和输注期间，每隔1小时采集母体血液和胎儿血液样本，以测定血浆PGE2、促肾上腺皮质激素（ACTH）和皮质醇浓度。尼美舒利处理的母羊在148±0 dGA时发生自然分娩，CONT组母羊在144±1 dGA时发生自然分娩。我们在分娩开始后9±2小时输注尼美舒利，在8±2小时输注溶媒。所有动物的母体和胎儿血气及pH值均保持不变。在CONT组母羊和胎儿中，输注溶媒前和输注期间所测的任何血浆激素浓度均未观察到显著变化。在尼美舒利处理的母羊中，母体血浆PGE2和ACTH浓度保持不变，而母体血浆皮质醇显著降低，3小时后恢复至基线水平。在尼美舒利处理的母羊的胎儿中，输注尼美舒利后，血浆PGE2和ACTH水平持续显著下降。胎儿血浆皮质醇显著降低，并在5小时后恢复至基线水平。这些结果表明：1）尼美舒利抑制PG合成在自然分娩期间对绵羊母体和胎儿下丘脑 - 垂体 - 肾上腺轴有不同影响；2）PG产生在绵羊胎儿下丘脑 - 垂体 - 肾上腺轴的调节中起生理作用。
