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The adrenal gland response to natural or synthetic adrenocorticotrophic hormone was studied at various periods after hypophysectomy. Adrenal ascorbic acid depletion was observed following the administration of ACTH at all intervals up to 10 days. In contrast, the capacity to respond to ACTH by an increase in corticosterone secretion was rapidly lost. Experiments with rat adrenal slices in vitro showed that the capacity to form corticosteroids following the addition of ACTH or 3′,5′-cyclic-AMP is rapidly lost after hypophysectomy, but that the adrenal slices are still capable of producing corticosterone if NADP and glucose-6-phosphate are added to the medium. It is concluded that the adrenal gland is still capable of responding to the action of ACTH for a considerable time after hypophysectomy, but that due to a metabolic block prior to the formation of NADPH, the adrenal is no longer capable of reacting by a further increase in corticosterone production. In addition, it was found that the effects of ACTH on blood flow and ascorbic acid output were parallel. Both effects were dose-dependent, but independent of any concomitant corticosterone secretion, and persisted during the whole period studied after hypophysectomy.

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