Aberrant GPCR expression is a sufficient genetic event to trigger adrenocortical tumorigenesis

Aberrant expression of G protein-coupled receptors (GPCR) in the adrenal cortex is observed in some cases of ACTH-independent macronodular adrenal hyperplasias and adenomas associated with Cushing syndrome (CS). Although there is clinical evidence for the implication of these receptors in abnormal regulation of cortisol secretion, whether this aberrant expression also directly causes the development of a benign adrenocortical tumor is an open question. Cell transplantation provides a way to study genes that may be important in human tumor development. The system we developed uses genetically modified adrenocortical cells transplanted into adrenalectomized immunodeficient mice, which form a functional tissue structure. We observed that enforcing expression of the gastric inhibitory polypeptide (GIP) receptor or the luteinizing hormone (LH) receptor genes (taken as canonical examples of aberrantly expressed GPCRs) in adrenocortical cells resulted in the formation of hyperplastic tissues and the development of Cushing syndrome features in transplanted mice. (c) 2006 Elsevier Ireland Ltd. All rights reserved.