Interaction between stimulus intensity and corticosteroid feedback in control of ACTH.

These studies were performed to examine the relationship between stimulus intensity and corticosteroid feedback on ACTH secretion. We have measured the ACTH responses in five dogs to each of three levels of hypoglycemia induced by injection of three doses of insulin after production of each of four levels of corticosteroid feedback induced by the infusion of saline or three rates of ACTH. Both the peak and integrated ACTH responses were related to the degree of hypoglycemia in saline-infused dogs (P less than 0.01). ACTH infusions did not affect the hypoglycemia induced by insulin; however, the lower two infusion rates (20 and 50 ng/min for 40 min) inhibited the peak ACTH responses to hypoglycemia by mean values of 45 and 75%, respectively, and the integrated ACTH responses by about 60 and 90%, respectively. The high infusion rate of ACTH (500 ng/min for 40 min) abolished the subsequent ACTH responses to hypoglycemia (103% inhibition). Therefore, the degree (%) of inhibition was the same for a given prior corticosteroid level at all intensities of hypoglycemia. The plasma ACTH response was a function of both stimulus intensity and prior corticosteroid levels and was proportional to the stimulus intensity divided by the feedback dose. Thus, corticosteroids exert a modulatory rather than a simple subtractive effect on the secretion of ACTH.