Ectopic and abnormal hormone receptors in adrenal cushing's syndrome

Abstract

Cortisol secretion mechanisms in the so-called primary adrenal Cushing's syndrome where ACTH level is lowered are unknown, and so far presumed to be due to an "autonomous" secretion. Nowadays, in vitro and in vivo studies by a number of investigators are successful in demonstrating that part of cortisol- and other steroid-producing adrenal tumors or hyperplasias are controlled by ectopic and/or aberrant membrane hormone receptors. The latter include ectopic receptors for gastric inhibitory polypeptide (GIP), β-adrenergic agonists, LH/hCG and eutopic receptors with impaired activity, such as the ones for vasopressin, serotonin and probably leptin. Usually these ectopic/aberrant receptors are functionally coupled to G-proteins, thereby activatinge adenyl cyclase and steroidogenesis. The molecular mechanisms to which these processes are attributed are still not well enough clarified. Their understanding may eventually lead to new pharmacological therapeutic approaches as an alternative to adrenalectomy. Thus far, a long-term control of ectopic β-adrenoreceptors and LH/hCG-dependent Cushing's syndrome is achieved by propranolol and leuprolide acetate. Further researches along this line will most likely identify a greater diversity of abnormal receptors in adrenals and other endocrine and nonendocrine tissues. Elucidation of the molecular mechanisms underlying abnormal hormone receptors expression will probably contribute to gain better insight into the the regulation of tissue-specific expression of genes.