INVOLVEMENT OF VASOPRESSIN AND CORTICOTROPIN-RELEASING HORMONE IN VIP-INDUCED AND PHI-INDUCED SECRETION OF ACTH AND CORTICOSTERONE

The relative roles of hypothalamic corticotropin-releasing-hormone (CR H) and vasopressin (AVP) as mediators of the stimulant effect of vasoa ctive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) on ACTH and corticosterone (CORT) secretion, were examined using recep tor blockade of endogenous CRH and AVP. ACTH and CORT secretion were s timulated 6- and 7-fold, respectively, by PVN infusion of VIP (3.0 nmo l) and 6- and 9-fold, respectively, by PHI (3.0 nmol). ACTH and CORT s timulation by VIP were inhibited 78 and 72%, respectively, by pretreat ment with the CRF antagonist, 59 and 57%, respectively, by pretreatmen t with the AVP antagonist and about 78% by combined pretreatment with the CRF and AVP antagonists. PHI-induced stimulation of ACTH and CORT was inhibited 89 and 81%, 73 and 59% and 93% by pretreatment with the CRF- or AVP-antagonist or combined administration, respectively. These results support the hypothesis that the activation of the hypothalami c-pituitary-adrenal (HPA) axis by VIP and PHI is mediated th rough the release of endogenous CRH. AVP also plays a role in this response, po ssibly by enhancing the activity of CRH in a synergistic manner.