title: [Ectopic secretion of ACTH and of related peptides (LPHs, beta-endorphin, "16K"). Evidence for a common precursor].
abstract: Studies in the experimental mouse pituitary tumor cell line AtT-20/D-16-v have recently shown that ACTH, the lipotropins (beta- and gamma-LPH), beta-endorphin (beta-End) and the 16-K fragment are synthesized through a common precursor molecule which is a 31,000 glycopeptide (pro-ACTH/endorphin). We have investigated whether such a biosynthetic model might exist in man. Radioimmunoassays have been developed against human ACTH, N-terminal LPH, beta-End or C-terminal beta-LPH, C-terminal gamma-LPH, and the 16-K fragment or N-terminal pro-ACTH/endorphin. These radioimmunoassays were used to examine various human samples before and after gel fractionation in ordinary or denaturing buffers. Medium DMS-79, in which human small cell carcinoma cells derived from a lung cancer were cultured, was shown to contain molecules identical to gamma-LPH, beta-LPH, beta-End and ACTH. In addition, it also contained a high molecular weight material with LPH, beta-End, and ACTH immunoreactivity. These three immunoreactivities could not be dissociated under denaturing conditions (6 M guanidine-HCl), and were all absorbed on an ACTH-purified anti-(1-24)-ACTH affinity column. Medium DMS-79 also contained high molecular weight calcitonin immunoreactivity that was not absorbed on the (1-24)-ACTH affinity column and therefore was not part of the pro-ACTH/endorphin molecule. Extracts from two pheochromocytomas responsible for the ectopic ACTH syndrome were found to contain, in addition to ACTH, large amounts of gamma-LPH and beta-End. High levels of beta-LPH and beta-End were also present in the plasma from a patient with the ectopic ACTH syndrome due to pancreatic carcinoma. Plasma immunoreactive 16-K fragment was increased in another patient with this syndrome. These results indicate that a biosynthetic model similar to that described in the AtT-20/D-16-v mouse tumor cell line also exists in man. Tumors responsible for the ectopic ACTH syndrome provide a unique source to study this model in man.
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis* / Q000378:metabolism*; D000818:Animals; D018288:Carcinoma, Small Cell; D002460:Cell Line; D003480:Cushing Syndrome / Q000378:metabolism; D004723:Endorphins / Q000096:biosynthesis* / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism; D010673:Pheochromocytoma / Q000378:metabolism; D010908:Pituitary Hormones, Anterior / Q000096:biosynthesis* / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011333:Pro-Opiomelanocortin; D011498:Protein Precursors / Q000096:biosynthesis* / Q000378:metabolism; D011863:Radioimmunoassay; D008083:beta-Lipotropin / Q000378:metabolism*
chemical_list: D004723:Endorphins; D010446:Peptide Fragments; D010908:Pituitary Hormones, Anterior; D011498:Protein Precursors; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D008083:beta-Lipotropin
vernacular_title: Sécrétion ectopique d'ACTH et de peptides apparentés (LPHs, beta-endorphine, "16K"). Mise en évidence d'un précurseur commun.