Control of canine ACTH by corticosteroids: interaction between dose and time

These experiments were designed to test for interactions between dose and time of administration of steroids in control of adrenocorticotropin hormone (ACTH). Five dogs were infused for 30 min with cortisol and corticosterone in a 2:1 ratio at a total rate of 1.5 or 3.0 micrograms.kg-1.min-1 beginning 120, 90, 60, 30, or 0 min before injection of insulin (0.5 U/kg). The infusions increased total plasma corticosteroids to approximately 50 or 80 ng/ml. Inhibition of basal ACTH occurred when infusion of steroid at either rate began greater than or equal to 60 min earlier. The degree of inhibition of stimulated ACTH was dependent on both steroid dose and timing of steroid infusion relative to the stimulus. Increasing corticosteroids to 50 ng/ml reduced the ACTH response to hypoglycemia if the infusion began 30 min, but not 60, 90, or 120 min earlier. Increasing corticosteroids to 80 ng/ml inhibited the response if the infusion began 120 or 60 min before injection of insulin. The data suggest that 1) inhibition of stimulated ACTH required less than or equal to 30 min to appear; 2) the duration of corticosteroid feedback is steroid-dose related; 3) basal ACTH secretion is more sensitive than stimulated ACTH to steroid inhibition; 4) small increments in plasma corticosteroids over short periods of time can inhibit canine ACTH.