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The mechanism by which cortisol is produced in adrenal Cushing’s syndrome, when ACTH is suppressed, was previously unknown and was referred to as being “autonomous.” More recently, several investigators have shown that some cortisol and other steroid-producing adrenal tumors or hyperplasias are under the control of ectopic (or aberrant, illicit, inappropriate) membrane hormone receptors. These include ectopic receptors for gastric inhibitory polypeptide (GIP), β -adrenergic agonists, or LH/hCG; a similar outcome can result from altered activity of eutopic receptors, such as those for vasopressin (V1-AVPR), serotonin (5-HT₄), or possibly leptin. The presence of aberrant receptors places adrenal cells under stimulation by a trophic factor not negatively regulated by glucocorticoids, leading to increased steroidogenesis and possibly to the proliferative phenotype. The molecular mechanisms responsible …