Expression of vasopressin receptors in ACTH-independent macronodular bilateral adrenal hyperplasia causing Cushing's syndrome: Molecular, immunohistochemical and pharmacological correlates

Abstract

Cortisol secretion in ACTH-independent macronodular adrenal hyperplasia (AIMAH) causing Cushing's syndrome can be controlled by illegitimate receptors. The aim of the present study was to characterize the molecular, immunohistochemical, and pharmacological profiles of vasopressin receptors in cells derived from three patients with AIMAH (H1-H3), in order to evaluate the role of ectopic vasopressin receptors in the physiopathology of hypercortisolism. Expression of mRNAs encoding the vasopressin receptor types (V1a, V1b, and V2) were analyzedby RT-PCR in adrenal tissues. The presence of V1a and V2 receptors was studied by immunohistochemistry on adrenal sections. The pharmacological profiles of vasopressin receptors involved in the control of cortisol secretion were investigated using the V1a receptor antagonist SR49059 and the V2 receptor agonist [deamino-Cys1, Val4, D-Arg8]-vasopressin on cultured cells. The V1a receptor protein was present and functional in H1 and H3 tissues, whereas the V1b receptor was not expressed in any of the tissues. RT-PCR experiments revealed that V2 receptor mRNAs were detected in the three tissues. In contrast, immunohistochemical and cell incubation studies showed that the V2 receptor was involved in the stimulatory eftect of AVP on cortisol secretion in H1 and H2, but not in H3 cells. Taken together, these data show that expression of functional ectopic V2 receptors and repression of eutopic V1a receptor can coexist in some hyperplastic corticosteroidogenic tissues. They also reveal that immunohistochemical and incubation studies are essential for the characterization of ectopic receptors actually involved in the control of cortisol secretion by AIMAHs. © 2008 Society for Endocrinology.