Studies in 80% Pancreatectomized Rats of the Synergistic Interaction of Growth Hormone, ACTH and the Glucocorticoids (Corticosterone, Cortisol, Prednisone and Dexamethasone) as Diabetogenic Agents
The diabetogenic effects of glucocorticoids, given alone or in combination with ACTH or bovine growth hormone (BGH), were studied in 80% pancreatectomized rats. The minimum effective daily dose (MED) of the glucocorticoids which would produce minimal glucosuria in 5 days was corticosterone, 10 mg; cortisol, 3 mg; prednisone acetate, 1 mg; and dexamethasone, 50 μg. Each of these glucocorticoids was injected in combination with BGH or ACTH to determine whether the combinations were additive or multiplicative (synergistic) in inducing glucosuria. Doses of hormone combinations were expressed as MEDs of the individual hormones. The effectiveness of cortisol was additive to that of BGH, whereas the other 3 glucocorticoids when combined with BGH showed a partial synergism, with dexamethasone showing the most synergism. Dexamethasone synergized with ACTH as perfectly as BGH does, whereas the other 3 steroids gave partial synergism. The 2 glucocorticoids, cortisol and dexamethasone, synergized when injected together. These synergism studies on the induction of glucosuria suggest that in the rat adrenal steroids other than corticosterone are produced under the influence of ACTH stimulation, and that they have a diabetogenic action differing from that of corticosterone itself. (Endocrinology88: 1429, 1971)