STUDIES ON THE POSSIBLE INHIBITORY EFFECT OF CORTICOSTERONE ON CORTICOSTEROIDOGENESIS AT THE ADRENAL LEVEL IN THE RAT1

Abstract

Following the subcutaneous administration of 5 nag. of corticosterone in the rat, the plasma level of this substance was maximal 1 and 2 hours following the injection. In spite of the highly elevated level of circulating corticosterone, no uptake of this substance occurred in the adrenals. The optimal amount of ACTH required to elicit a maximum elevation of adrenal corticosterone two hours after its subcutaneous injection was 2 units. Two hours after the simultaneous administration of 2 units of ACTH and 5 mg. of corticosterone in the intact rat the mean adrenal corticosterone was lower than when 1 units of ACTH were administered alone. When the experiment was repeated with 4 units of ACTH being injected the mean adrenal corticosterone was significantly lower (P< 0.01). Repetition of these experiments with ACTH or ACTH plus corticosterone-pretreated hypophysectomized rats indicated that the corticosteroidogenic effect of ACTH was decreased. No ACTH response was observed in rat adrenal sections when these were incubated in vitro with 20 ug. of corticosterone and 50 milliunits of ACTH. The experiments suggest that the circulating levels of blood corticosterone in the rat may control its production by acting directly on the adrenal gland by inhibiting the action of ACTH.