title: Unrestrained production of proopiomelanocortin (POMC) and its peptide fragments by pituitary corticotroph adenomas in Cushing's disease.
abstract: The hallmark of ACTH oversecretion in Cushing's disease is its partial resistance to the normal suppressive effect of glucocorticoids. Because ACTH secretion by the pituitary tumor is not normally restrained ACTH is overproduced with subsequent chronic hypercortisolism. Since peripheral tissues have retained their normal sensitivity to the action of cortisol they appropriately develop the features of Cushing's disease. The question of whether a collection of corticotroph cells, eventually arranged in an adenomatous-like fashion, is a primary pituitary event or is corticotropin-releasing factor driven has had no response so far. Clonal composition of such lesions has been determined by X chromosome inactivation using DNA probes which detect multiallelic polymorphism in females. A monoclonal pattern is found in all macroadenomas. ACTH is co-secreted with other peptide fragments derived from their common polypeptide precursor, proopiomelanocortin (POMC). As a rule POMC processing in pituitary tumors is qualitatively unaltered: plasma values of the N-terminal fragment, the joining peptide, the beta- and gamma-lipotropins, and beta-endorphin all are valid alternate markers of the tumor activity. Tumor POMC peptides including ACTH and its phosphorylated form usually show no peculiar or unexpected molecular forms in contrast with what is often found when POMC expression occurs in a non-pituitary tumor.
authors.affiliation: Centre de Recherche sur les Maladies Endocriniennes, CHU Cochin, Paris, France.
authors.forename: X
authors.initials: X
authors.lastname: Bertagna
mesh_terms: D000236:Adenoma / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D003480:Cushing Syndrome / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone