Eutopic Overexpression of Vasopressin V1a Receptor in Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia

Arginine vasopressin (AVP) stimulates cortisol secretion through its vascular type V1a receptor in the adrenal glands, in addition to stimulating ACTH secretion through pituitary V3 receptor. Because hyper-response of plasma cortisol to vasopressin is documented in some patients with Cushing’s syndrome due to adrenal adenoma (CS) or ACTH-independent macronodular adrenocortical hyperplasia (AIMAH), we analyzed the expression of V1a, V2, V3 receptor and AVP mRNA in human adrenal tissues by quantitative competitive RT-PCR or real-time PCRs. V1a receptor mRNA levels (ratio against glyceraldehyde 3-phosphate dehydrogenase) were 0.378 ± 0.143 (mean ± se) in preclinical CS (n = 5) and 0.630 ± 0.072 in AIMAH (n = 4), which were significantly higher than those (0.046 ± 0.012; n = 9) in control adrenals, whereas those in overt CS (0.143 ± 0.048; n = 10) or aldosterone-producing adenomas (0.069 ± 0.018; n = 12) were similar to control adrenals. Although ectopic expression of V2 or V3 receptor was detected in half of...