Negative, Rate-Sensitive Feedback Effects on Adrenocorticotrophin Secretion by Cortisol in Normal Subjects

Plasma ACTH and corticosteroid levels were measured in normal subjects during constant infusion of either 0.9% (W/V) NaCl solution or cortisol, and during insulin-induced hypoglycaemia. During infusions of 0.9% NACl solution the secretion of ACTH and corticosteroids was episodic. Fast, rate-sensitive, negative feedback inhibition of ACTH secretin was observed during cortisol infusions, when the corticosteroid levels were within the physiological range (200-750 nmol/l) and were rising at a rate of between 5 and 10 nmol/l per min for 30 min or longer. When plasma corticosteroid levels were in a steady state, the initial fast feedback effects were abolished and ACTH secretion resumed. However, this recovery of ACTH secretion was not seen when the corticosteroid levels were persistently above 800 nmol/l. It appears that corticosteroid-induced negative feedback in man may be both rate- and level-sensitive. During insulin stress test ACTH secretion fell at time when the plasma corticosteroid level was rising rapidly (greater than 5 nmol/1 per min) despite persistent hypoglycaemia.