Vasopressin receptors modulate the pharmacological phenotypes of Cushing'ssyndrome

We have examined the expression profiles of the different vasopressin recep tors (V-1, V-2, V-3) that can be expressed in the three different types of tumors associated with Gushing's syndrome. V-3 (V-1b) receptor cDNA was clo ned from a pituitary tumor responsible for Gushing's disease. We show that it is overexpressed in these tumors and can respond to DD-AVP. High express ion of the V-3 receptor on highly differentiated, ACTH-secreting, bronchial carcinoid tumors explain why these non-pituitary tumors occasionally respo nd to vasopressin, mimicking a "pituitary-like" behavior. A retrospective a nalysis showed that vasopressin induced an ACTH-independent cortisol rise i n 27% of the adrenocortical tumors responsible for Gushing's syndrome. V1 m RNA was detected in normal adrenal cortex and in all tumors. Adenomas had s ignificantly higher levels than carcinomas. V-1 mRNA levels were higher in responders than in non-responders. One adenoma which had a brisk cortisol r esponse in vivo, also had in vitro cortisol responses that were inhibited b y a specific V1 antagonist. In situ hybridization showed the presence of V- 1 mRNA in the normal human adrenal cortex where the signal predominated in the compact cells of the zona reticularis. A positive signal was also prese nt in the tumors with high V1 mRNA levels determined by RT-PCR; its distrib ution pattern was heterogeneous and showed preferential association with co mpact cells. High-and not ectopic-expression of the V-1 receptor occurs in a minority of adrenal cortical tumors which become directly responsive to v asopressin stimulation.