Cortisol infusion depresses the ratio of bioactive to immunoreactive ACTH in adrenalectomized sheep fetuses

We examined the effects of exogenous cortisol on plasma immunoreactive adrenocorticotropic hormone (iACTH), bioactive ACTH (bACTH), and ACTH-(1-39) in nine adrenalectomized fetuses at 126-130 and 136-140 days of gestation. Fetuses received 4 h of cortisol (2 micrograms.kg-1.min-1) or saline infusions on consecutive days. Blood was obtained before and at intervals during infusions. Arterial blood gases and hematocrits were normal and did not change with age. Plasma cortisol did not change during saline infusions but increased significantly (range 30-70 ng/ml) during cortisol infusions. Basal plasma iACTH, bACTH, ACTH-(1-39), and bACTH-to-iACTH and ACTH-(1-39)-to-iACTH ratios were significantly higher in the older fetuses. Cortisol infusions decreased plasma iACTH, bACTH, and ACTH-(1-39) in both groups, and the suppression as a percent of the baseline was similar. The bACTH-to-iACTH ratio declined to the same level at 126-130 (0.201 +/- 0.040 to 0.051 +/- 0.002) and 136-140 (0.389 +/- 0.088 to 0.046 +/- 0.002) days of gestation. These data suggest that physiological concentrations of cortisol selectively inhibit bACTH secretion, and the ACTH response to cortisol inhibition is not different between 126 and 140 days of gestation in adrenalectomized sheep fetuses.