Adrenal responses to prostaglandin E2 in newborn lambs

Prostaglandin E2 (PGE2) is present in fetal sheep and stimulates adrenal steroidogenesis in the fetal and newborn sheep. We have examined the site of this prostaglandin effect and the changes in adrenal responsiveness to exogenous PGE2 and adrenocorticotropic hormone (ACTH) in in vivo studies with newborn lambs. A bolus injection of PGE2 (50 micrograms) into the brachiocephalic trunk or descending aorta raised plasma cortisol (F) 25.3 +/- 4.5 (SE) ng/ml to 75.5 +/- 5.4 ng/ml at 15 to 30 minutes and 23.2 +/- 3.0 to 60.5 +/- 7.1 ng/ml at 15 to 30 minutes, respectively (both P less than 0.001). Intra-aortic infusion of PGE2 (1.25 micrograms/ml) produced a similar significant rise in F. Basal plasma F decreased from 34.3 +/- 7.4 ng/ml at 9 to 11 days to 14.1 +/- 4.0 ng/ml at 12 to 13 days and 18.2 +/- 5.7 ng/ml at 17 to 18 days. Peak F during a 60-minute PGE2 infusion was significantly greater at 9 to 11 days (127.3 +/- 14.6 ng/ml) than at the two later times (57.2 +/- 7.07 and 55.7 +/- 14.6 ng/ml, respectively, both P less than 0.01). The response to ACTH was greater 24 hours after birth than at 7 or 28 days of age. Injection of ACTH or alpha-melanocyte-stimulating hormone during an intra-aortic PGE2 infusion did not further elevate plasma F over the rise seen with PGE2 alone. The results suggest both direct and indirect stimulatory effects of PGE2 on adrenal function in newborn sheep, and are consistent with a role of endogenous PGE2 as an intermediate factor in ACTH action.