Adrenocorticotropin receptor and adrenal disorders

Hormone Research
B Allolio, M Reincke

Abstract

The ACTH receptor is the shortest G-protein-coupled receptor to date and consists of 297 residues with two putative glycosylation sites at the extracellular N terminus. In vitro studies have demonstrated upregulation of the ACTH receptor by its own ligand and by angiotensin II. Inactivating mutations of the ACTH receptor lead to the familial glucocorticoid deficiency (FGD) syndrome, a rare recessive autosomal disorder characterized by degeneration of the zona fasciculata/reticularis and unresponsiveness to exogenous ACTH. Interestingly, ACTH receptor mutations are not present in all patients with FGD and also not in the closely related "triple A' syndrome indicating that other mechanisms of ACTH resistance are still to be elucidated. Despite an extensive search, no activating ACTH receptor mutations have been found in adrenal tumors, excluding the ACTH receptor as a relevant oncogene for adrenal tumorigenesis. However, the ACTH receptor may play a role as a differentiation factor, as loss of heterozygosity for the ACTH receptor in adrenal tumors seems to be associated with an undifferentiated phenotype. ACTH receptor mRNA expression in benign adrenal tumors is strongly related to the expression of P-450 side chain cleavage enzy...Continue Reading

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