Does reduction of circulating prostaglandin E2 reduce fetal hypothalamic-pituitary-adrenal axis activity?

OBJECTIVE: Placental production of prostaglandin E2 (PGE2) increases in fetal sheep as term approaches. It has been suggested that placental PGE2 may act as a hormone to activate the fetal hypothalamic-pituitary-adrenal (HPA) axis. Alternatively, we have proposed that local generation of prostaglandins in the fetal brain and/or pituitary might play a more prominent role in the stimulation of fetal adrenocorticotropin (ACTH) secretion. We performed the present experiments to test the hypothesis that the elevated concentrations of PGE2 in fetal plasma do not tonically stimulate fetal ACTH secretion.
METHODS: We studied chronically catheterized late-gestation fetal sheep. Selective inhibitors of prostaglandin synthase-1 and -2 (PGHS-1 and PGHS-2) were injected intravenously. Fetal blood pressure and heart rate were monitored continuously, and circulating concentrations of PGE2, ACTH, and cortisol were measured by specific immunoassay.
RESULTS: Injection of vehicle did not have an effect on circulating levels of PGE2 or ACTH, but it did have a mild stimulatory effect on cortisol. The selective PGHS-2 inhibitor, Nimesulide (Cayman Chemical, Ann Arbor, MI), significantly decreased plasma PGE2 concentrations. The selective PGHS-1 inhibitor, Resveratrol (Cayman Chemical), produced smaller decreases in plasma PGE2 concentrations and significantly increased mean arterial blood pressure. Neither inhibitor significantly altered plasma ACTH or cortisol concentrations.
CONCLUSION: These results demonstrate that reduction of circulating PGE2 concentrations in response to intravenous injection of PGHS-1 and PGHS-2 inhibitors does not reduce fetal HPA axis activity. We conclude that PGE2 in late-gestation ovine fetal plasma does not tonically stimulate fetal ACTH secretion.