Expression of vasopressin receptors in ACTH-independent macronodular bilateral adrenal hyperplasia causing Cushing's syndrome: molecular, immunohistochemical and pharmacological correlates.
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 (V(1a), V(1b), and V(2)) were analyzed by RT-PCR in adrenal tissues. The presence of V(1a) and V(2) 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 V(1a) receptor antagonist SR49059 and the V(2) receptor agonist [deamino-Cys(1), Val(4), D-Arg(8)]-vasopressin on cultured cells. The V(1a) receptor protein was present and functional in H1 and H3 tissues, whereas the V(1b) receptor was not expressed in any of the tissues. RT-PCR experiments revealed that V(2) receptor mRNAs were detected in the three tissues. In contrast, immunohistochemical and cell incubation studies showed that the V(2) receptor was involved in the stimulatory effect of AVP on cortisol secretion in H1 and H2, but not in H3 cells. Taken together, these data show that expression of functional ectopic V(2) receptors and repression of eutopic V(1a) 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.
Louiset
E
E
INSERM U413, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research (IFRMP 23), University of Rouen, 76821 Mont-Saint-Aignan, France.
Contesse
V
V
Groussin
L
L
Cartier
D
D
Duparc
C
C
Perraudin
V
V
Bertherat
J
J
Lefebvre
H
H
D000307:Adrenal Gland Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology; D000311:Adrenal Glands / Q000737:chemistry / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000502:physiology; D000328:Adult; D001127:Arginine Vasopressin / Q000494:pharmacology; D002478:Cells, Cultured; D003480:Cushing Syndrome / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006965:Hyperplasia; D007150:Immunohistochemistry; D008875:Middle Aged; D009384:Paraneoplastic Endocrine Syndromes; D012333:RNA, Messenger / Q000032:analysis; D017483:Receptors, Vasopressin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone