Adenosine 3′,5′-Monophosphate as the Mediator of ACTH-Induced Ascorbic Acid Depletion in the Rat Adrenal

Rats were hypophysectomized, and 2 hr later one adrenal was excised. An intravenous infusion was then carried out for 1 hr followed by the removal of the remaining adrenal. Assay of the 2 adrenals revealed that infusion of 30 mg dibutyryl cyclic AMP resulted in a decrease in ascorbic acid concentration of 20±2% (mean±SEM, 17 rats), while 5 U of ACTH produced a decrease of 28±3% (11 rats). Saline controls exhibited an increase of 6±3%. During 1-hr incubations of rat adrenals, 10 mM cyclic AMP produced a 13±3% decrease in ascorbic acid levels, a result similar to that produced by ACTH. These results suggest that cyclic AMP mediates the ascorbic acid depleting effect of ACTH. Cycloheximide in quantities sufficient to block adrenal protein synthesis and the stimulation of steroidogenesis also impaired the ascorbic acid depleting effects of ACTH and cyclic AMP in vivo and in vitro. An NADPH generating system produced a significant increase in corticosterone production, but failed to bring about ascorbic acid release in vitro. (Endocrinology87: 118, 1970)