Role of Glucose in Facilitating the Acute Steroidogenic Action of Adrenocorticotropic Hormone (ACTH)

The possible role of glucose in facilitating the steroidogenic action of ACTH was investigated. In studies with quartered rat adrenals, reducing the glucose concentration from 10 to 1 mM significantly reduced the amount of cyclic AMP formed in response to ACTH and significantly reduced the amount of corticosterone formed in response to either ACTH or cyclic AMP but did not diminish the amount of corticosterone formed in response to exogenous NADPH or progesterone. In the presence of 10 mM glucose, stimulation of corticosterone synthesis with ACTH or cyclic AMP was accompanied by parallel increases in glucose oxidation, but stimulation of corticosterone synthesis by the addition of NADPH or progesterone was not accompanied by increased glucose oxidation. Adrenal homogenates failed to respond to ACTH or cyclic AMP with increases in corticosterone production or glucose oxidation; such preparations responded to NADPH with increases in corticosterone production but without increased glucose oxidation. One role of glucose in facilitating the steroidogenic action of ACTH might be to facilitate the formation of cyclic AMP, the intracellular mediator of the action of ACTH. Since cyclic AMP-dependent steroidogenesis is facilitated by glucose and NADPH-dependent steroidogenesis is not, it is concluded that an additional role of glucose might be to serve as a substrate in some biochemical reaction that is accelerated by cyclic AMP, possibly the generation of compartmentalized NADPH.