PROSTAGLANDIN REGULATION OF FETAL PLASMA ADRENOCORTICOTROPIN AND CORTISOL CONCENTRATIONS IN LATE-GESTATION SHEEP

It is widely recognized that prostaglandins (PGs) are involved in regu lation of the hypothalamo-pituitary-adrenal axis and that the activati on of the fetal hypothalamo-pituitary-adrenal axis plays a central rol e in the process of labor in sheep. However, effects of inhibition of PG synthesis on the maternal and fetal hypothalamo-pituitary-adrenal a xis during parturition have not been characterized. We examined the ef fect of inhibiting PC synthesis on the maternal and fetal hypothalamo- pituitary-adrenal axes during spontaneous term labor by using nimesuli de, a PGH synthase (PGHS) inhibitor. Under halothane anesthesia, eight pregnant ewes were instrumented with vascular catheters and myometria l electromyogram (EMG) electrodes at 127 +/- 3 (mean +/- SEM) days ges tation (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 3 0 mg/h). Vehicle was infused to the remaining four ewes (controls, CON T). Maternal blood and fetal blood were sampled at 1-h intervals befor e and during infusion to determine plasma PGE(2), ACTH, and cortisol c oncentrations, Spontaneous labor occurred at 148 +/- dGA in nimesulide -treated ewes and at 144 +/- dGA in CONT ewes, We infused nimesulide f rom 9 +/- 2 h and vehicle from 8 +/- 2 h after the onset of labor. Mat ernal and fetal blood gases and pH remained unchanged in all animals. No significant changes were observed in any plasma hormone concentrati ons measured in CONT ewes and fetuses before and during vehicle infusi on. in nimesulide-treated ewes, maternal plasma PGE(2) and ACTH concen trations remained unchanged, white maternal plasma cortisol decreased significantly, recovering to baseline by 3 h. In fetuses of nimesulide -treated ewes, plasma PGE(2) and ACTH levels showed significant sustai ned decreases after nimesulide infusion. Fetal plasma cortisol decreas ed significantly and returned to baseline by 5 tl. These results sugge st that 1) PG synthesis inhibition by nimesulide has differential effe cts on the ovine maternal and fetal hypothalamo-pituitary-adrenal axes during spontaneous labor, and 2) PC production plays a physiologic ro le in regulation of the ovine fetal hypothalamo-pituitary-adrenal axis .