Prostaglandin regulation of fetal plasma adrenocorticotropin and cortisol concentrations in late-gestation sheep

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.