IMPAIRMENT OF THE PITUITARY-ADRENAL RESPONSE TO ACUTE STRESS IN ALLOXAN DIABETES

ABSTRACT The adrenal ascorbic acid depletion parameter was used to determine the pituitary-adrenal response to acute stress, the adrenal responsiveness to exogenous corticotrophin (ACTH), and the pituitary ACTH reserve in alloxan diabetes. The pituitary-adrenal response to histamine (0.5 mg/100 g i. p.) 1 hour before sacrifice was significantly impaired in uncontrolled diabetes. Elimination of glycosuria by insulin administration (7 days) restored the response to normal though adrenal hyperplasia was still evident. The impaired stress response was not due to a decrease in the adrenal responsiveness or the pituitary ACTH reserve. The adrenal ascorbic acid depletion response to exogenous ACTH (measured against saline controls) was normal. Pituitary extracts of diabetic animals produced the same degree of adrenal ascorbic acid depletion in hypophysectomized animals as pituitary extracts of normal animals. The adrenal hyperactivity previously reported to exist in uncontrolled diabetes is accompanied by a decreased ability to release preformed ACTH in response to acute stress. The metabolic stress of diabetes resembles other chronic stressors which impair the secretory mechanism at the hypothalamo-hypophyseal level.