Vasoactive intestinal peptide stimulates adrenocorticotropin release from human corticotropinoma cells in culture: interaction with arginine vasopressin and hydrocortisone.

The effect of vasoactive intestinal peptide (VIP), cholecystokinin octapeptide (CCK), bombesin, arginine vasopressin (AVP), and hydrocortisone (HC) on ACTH release from human corticotropinoma cells in culture has been studied. Tumor tissue was obtained from 6 patients with pituitary corticotropinomas. Eleven to 21 cultures yielding 0.7-2.0 X 10(6) cells/culture, were obtained from each tumor and maintained for periods of 4 weeks to longer than 6 months. VIP (500 ng/ml) significantly (P less than 0.005) stimulated ACTH release from all tumors studied, and a dose (5-500 ng/ml)-response effect was observed in 3 of 5 tumors. Stimulation by VIP was seen at 2,4, and 24 h and was maximal at 4 h. CCK and bombesin were without effect on ACTH release from 4 tumors studies at 4 h. AVP (1-10 mU/ml) stimulated ACTH from 4 tumors studied at 60 min or 4 h. Coincubation of cultures with VIP (50-500 ng/ml) and AVP (1-10 mU/ml) resulted in at least an additive effect. HC (100 ng/ml) significantly (P less than 0.025) inhibited basal ACTH secretion from 2 of 4 tumors at 4 h and from 3 of 4 (P less than 0.005) at 24 h. Simultaneous coincubation of cultures with VIP (50 ng/ml) and HC (100 ng/ml) resulted in an attenuation or blockade of the VIP-stimulated ACTH release, whereas prior incubation of cultures with HC for 28 h before exposure to VIP did not. The results demonstrate that VIP is a potent ACTH secretagogue from human corticotropinoma cells in culture; its effects are additive to those of AVP and modulated by HC.