Role of epinephrine and vasopressin in the control of the pituitary-adrenal response to stress

Abstract

In addition to corticotropin-releasing factor (CRF) and structurally related peptides, arginine vasopressin (AVP), oxytocin, angiotensin II, vasoactive intestinal polypeptide, peptide histidine isoleucinamide, epinephrine (E), and norepinephrine induce secretion of adrenocorticotropin (ACTH) from corticotropic cells in vitro. The apparent affinity and intrinsic ACTH-releasing activity of these substances are lower than those of CRF. These substances can also act synergistically with CRF. In this paper the role of catecholamines and AVP in the control of ACTH release is discussed. Infusion i.v. of E increases plasma ACTH and corticosterone to levels that are normally found during stress. E-induced stimulation of pituitary-adrenal activity is mediated by beta adrenoceptors and involves release of CRF, because it can be prevented by beta-adrenoceptor blockers and by destruction of CRF neurons (hypothalamic lesions), blockade of CRF release (chlorpromazine, morphine, and Nembutal), or administration of CRF antiserum. Although stress can cause a vast increase in plasma E, circulating E is not essential for the acute stress-induced release of ACTH because blockade of beta (or alpha) adrenoceptors, administration of chlorisondamine, or extirpation of the adrenal medulla and sympathectomy do not prevent the pituitary-adrenal response to stress. In contrast, circulating E plays a major role in the release of intermediate-lobe peptides during emotional stress. Studies of the role of AVP in pituitary-adrenal control by the use of pressor receptor (V1) antagonists are not valuable because of the ineffectiveness of such antagonists in blocking AVP-induced release of ACTH from corticotropic cells in vitro. Treatment of rats with an antiserum to AVP reduces the ACTH response to stress. We conclude that AVP has an important role in stress-induced activation of the pituitary-adrenal system, possibly by potentiating the effects of CRF.