The dynamics of adrenocortical secretion

Abstract

The rate of cortisol secretion by the perfused canine adrenal was measured as ACTH was added to the perfusing blood according to various temporal patterns. The resulting concentrations of ACTH in adrenal arterial blood approximated 1 of the following time functions: single pulse, stepwise increase, stepwise decrease, and sinusoids of different frequency. When ACTH concentration was increased stepwise from 0 to 2 [mu]U/ml, cortisol secretion rate began to increase after a 2 min. delay, reached a peak at 8-13 min., and then declined gradually over the next 25-30 min. to a value which was steady thereafter. The peak secretion rate during this overshooting response was a mean of 165% of the final steady-state secretion rate, whose mean was 2.2 [mu]g/min. Following the the stepwise reduction in ACTH concentration from 2 to 1 or 0 [mu]U/ml, cortisol secretion rate declined monotonically with an apparent time constant of approximately 3 min. When ACTH concentration was reduced from 2 [mu]U/ml to 0 and then after 5 min. returned to 2 [mu]U/ml, cortisol output declined and then returned to its original value without overshoot, but when 40 min. separated these changes in ACTH level, cortisol secretion rate returned to its original value with overshoot. An increase in ACTH concentration from 0 to 30 or 70 [mu]U/ml was followed by a rapid increase in cortisol secretion rate to near-maximal values, without overshoot. The results with sinusoidal variations in ACTH concentration suggested that an apparent 3 min. time constant is dominant in the adrenal response to ACTH. Two dynamic models for the adrenocortical response to ACTH are offered. Both models simulate the experimental results and are systems of conservation equations for known and postulated biochemical intermediates in the coupling between ACTH and cortisol biosynthesis.