The ACTH-releasing activity of two stimuli, lysine vasopressin and epinephrine, was studied at time intervals ranging up to three days after beginning dexamethasone administration. Male rats were given a large pulse dose of dexamethasone to suppress ACTH secretion and the suppression was continued by the administration of dexamethasone in the drinking water. At intervals thereafter, the rats received graded doses of vasopressin or epinephrine. Twenty minutes later, blood was taken for corticosterone determination. The plasma corticosterone response to both stimuli fell progressively with longer durations (and cumulative total amount) of dexamethasone pretreatment. However, the greater the stimulus applied, the longer was the period of time required for suppression of the plasma corticosterone response. While adrenocortical responsiveness to exogenous ACTS also diminished with time, diminished adrenocortical responsiveness alone did not account for the depressed responses to the stimuli as evidenced by the fact that vasopressin-induced increases in plasma ACTH concentration also fell progressively after beginning dexamethasone. Pituitary ACTH content was not significantly affected by the dexamethasone administration. It is concluded that both the duration of prior corticosteroid administration and the intensity of an ACTH-releasing stimulus are important determinants of pituitary-adrenal activation.
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