Fast feedback control of canine corticotropin by cortisol.

These experiments test whether the rapid inhibition of ACTH responses in dogs fits the criterion for fast feedback. The ACTH response to hypoglycemia was measured after infusion of vehicle or cortisol at a rate of 9 or 18 micrograms/kg.min beginning at the time of injection of insulin or after infusion of 18 micrograms/kg.min beginning 20, 30, or 60 min later. Plasma ACTH was increased from 30-90 min after insulin treatment in all experiments. The ACTH responses to hypoglycemia were inhibited by cortisol infusions of 9 or 18 micrograms/kg.min beginning at 0 min [mean ACTH from 30-90 min: after vehicle, 557 +/- 57 (+/- SEM); after cortisol, 221 +/- 20 and 201 +/- 48 pg/ml, respectively], but the overall responses were not significantly reduced by infusions beginning 20, 30, or 60 min after the injection of insulin. The latency of the inhibition was 30 min after the infusions beginning at 0 min and 40-50 min after cortisol infusions beginning at later times. The infusion of cortisol also significantly reduced basal ACTH; however, this inhibition was not significant until 40 min. In further experiments the ACTH response to insulin-induced hypoglycemia was measured after infusing 45 micrograms/kg cortisol over 2, 5, or 15 min at rates of 22.5, 9, or 3 micrograms/kg.min. These infusions caused suppression of plasma ACTH by 30 min, but there was no significant difference in the degree of suppression (mean ACTH from 30-90 min: after vehicle, 532 +/- 34; cortisol for 2 min, 223 +/- 34; cortisol for 5 min, 197 +/- 18; cortisol for 15 min, 181 +/- 36 pg/ml). Thus, the inhibition of stimulated ACTH secretion in the dog is dependent on the feedback signal occurring at the initiation of the stimulus, but is not related to the rate of increase in plasma cortisol.