Abnormal regulation of adrenal function in rats with streptozotocin diabetes.

The factors that control adrenal steroid secretion and metabolism were investigated in rats made diabetic with Streptozotocin (65 mg/kg) and used one month after treatment. Diabetic animals possessed high resting levels of plasma corticosterone accompanied by adrenal hypertrophy; the showed an increased response to the stress of i.p. cold water injection. Moreover, the pituitaries of diabetic rats seemed to be releasing ACTH continuously and not storing it. Upon adrenal inhibition with Aminoglutethimide the expected increase in adrenal cholesterol and weight was of a smaller magnitude than in controls. The activity of liver enzymes that reduce ring A of corticosterone showed decreased activity in diabetics, which suggests that more corticosterone rather than its inactive metabolites were available to--but not able to suppress--the steroid feedback sites. The half-life of corticosterone in blood was similar in diabetes and controls. These results suggest that (a) diabetic animals were in a chronic stress condition; (b) the threshold for steroid feedback was less sensitive to variations in plasma corticosterone; (c) there is an abnormal peripheral disposal of corticosterone, but that other factors, besides the liver, regulate the clearance of the hormone from the circulation in the diabetic animals.