The adrenal cortex and the metabolic response to stress.

Abstract

SINCE the development of the concepts of the “alarm reaction,” the “general adaptation syndrome” and the “diseases of adaptation” by Hans Selye (1), there has been a great deal of interest in; and considerable controversy about the precise role of the adrenal cortex in the response to stress. That there is an intimate relationship between the adrenal cortex and the response to stress is well established on the basis of the following facts: (a) After stressful stimuli, there are unmistakable evidences in most cases of adrenocortical stimulation comparable with that after treatment with corticotropin. These include morphologic changes in the adrenal cortex, depletion of adrenal ascorbic acid and cholesterol, adrenal hypertrophy and, in many cases, increased levels of adrenal steroids in adrenal venous or peripheral venous blood and in the urine, (b) Many of the morphologic and metabolic alterations after stress in the normal organism are identical with those following overdosage with corticotropin or 11-oxygenated steroids. These include lymphopenia and eosinopenia, involution of lymphoid tissue and thymus, negative nitrogen, potassium and phosphate balances, sodium and chloride retention and impaired carbohydrate tolerance and insulin resistance, (c) In the absence of the adrenal cortex or pituitary, there is extreme sensitivity to stress, with metabolic and circulatory decompensation; in general, the foregoing morphologic and metabolic reactions do not occur, (d) As shown by Richter (2) and his collaborators, animals such as wild rats, which lead a continuously stressful existence, have very large adrenal glands. Presumably, these glands are under maximal or nearly maximal pituitary stimulation, since they do not exhibit ascorbic acid depletion in response to corticotropin injection or surgical trauma. Furthermore, such animals do not readily survive adrenalectomy, even with substitution therapy adequate for domestic rats (2,3).