Insensitivity of near-term fetal sheep to cortisol: possible relation to the control of parturition

In ruminants, parturition is stimulated by increased cortisol secretion by the fetal adrenal in the last few days of fetal life. Before this preparturient surge in fetal plasma cortisol, fetal ACTH and renin secretion are suppressed by small physiological increases in the fetal plasma cortisol concentration. The purpose of this study was to investigate the possibility that the sensitivity of ACTH and renin to cortisol inhibition is reduced at term. Fetal sheep, chronically catheterized at least 4 days before the first experiment, were subjected to iv infusion of cortisol at rates of 0 (n = 5), 1 (n = 4), 2 (n = 4), 5 (n = 5), and 10 (n = 5) micrograms/min for 5 h. One hour after the end of the cortisol infusion, fetal ACTH secretion was stimulated by fetal iv infusion of sodium nitroprusside (50 micrograms/min). In all groups, fetal plasma ACTH increased during the cortisol infusions, perhaps reflecting a circadian variation in fetal ACTH secretion which was not suppressed by cortisol. The endogenous increase in fetal ACTH during cortisol infusions produced apparently nonsteady state changes in fetal plasma cortisol concentrations. Cortisol infusion produced dose-related increases in the fetal plasma cortisol concentration. The highest rate of cortisol infusion increased fetal plasma cortisol to between 50 and 60 ng/ml. However, none of the cortisol infusions significantly suppressed fetal PRA or reduced the magnitude of the ACTH response to nitroprusside. The results demonstrate that acutely stimulated fetal ACTH secretion is not regulated by cortisol negative feedback in the last few days of fetal life. Reduction in negative feedback efficacy may allow the preparturient rise in cortisol secretion that is responsible for stimulating parturition in this species.