Vasopressin receptors modulate the pharmacological phenotypes of Cushing's syndrome.
We have examined the expression profiles of the different vasopressin receptors (V1, V2, V3) that can be expressed in the three different types of tumors associated with Cushing's syndrome. V3 (V1b) receptor cDNA was cloned from a pituitary tumor responsible for Cushing's disease. We show that it is overexpressed in these tumors and can respond to DD-AVP. High expression of the V3 receptor on highly differentiated, ACTH-secreting, bronchial carcinoid tumors explain why these non-pituitary tumors occasionally respond to vasopressin, mimicking a "pituitary-like" behavior. A retrospective analysis showed that vasopressin induced an ACTH-independent cortisol rise in 27% of the adrenocortical tumors responsible for Cushing's syndrome. V1 mRNA was detected in normal adrenal cortex and in all tumors. Adenomas had significantly higher levels than carcinomas. V1 mRNA levels were higher in responders than in non-responders. One adenoma which had a brisk cortisol response in vivo, also had in vitro cortisol responses that were inhibited by a specific V1 antagonist. In situ hybridization showed the presence of V1 mRNA in the normal human adrenal cortex where the signal predominated in the compact cells of the zona reticularis. A positive signal was also present in the tumors with high V1 mRNA levels determined by RT-PCR; its distribution pattern was heterogeneous and showed preferential association with compact cells. High-and not ectopic-expression of the V1 receptor occurs in a minority of adrenal cortical tumors which become directly responsive to vasopressin stimulation.
Arnaldi
G
G
Groupes d'Etude en Physiopathologie Endocrinienne, UPR-CNRS 1524 and Institut Cochin de Génétique Moléculaire, Paris, France.
de Keyzer
Y
Y
Gasc
J M
JM
Clauser
E
E
Bertagna
X
X
D000306:Adrenal Cortex Neoplasms / Q000378:metabolism; D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism; D001984:Bronchial Neoplasms / Q000378:metabolism; D002276:Carcinoid Tumor / Q000378:metabolism; D003480:Cushing Syndrome / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis; D007536:Isomerism; D010641:Phenotype; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism / Q000502:physiology*; D014667:Vasopressins / Q000494:pharmacology
D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D014667:Vasopressins; D011333:Pro-Opiomelanocortin; D006854:Hydrocortisone