adrenomedullin and Carcinoid-Tumor

To study the expression of adrenomedullin, a potent vasodilator peptide originally isolated from a pheochromocytoma, in ectopic ACTH-secreting tumors.. Tumor tissue concentrations of adrenomedullin, calcitonin gene-related peptide, neuropeptide Y, endothelin-1, corticotropin-releasing hormone and ACTH were measured in three ectopic ACTH-secreting tumors by RIA. The expression of adrenomedullin mRNA was examined by northern blot analysis of tissue from one of the tumors.. Immunoreactive adrenomedullin was detected in tumor tissues of three ectopic ACTH-secreting tumors (0.60-18.5 pmol/g wet weight). Calcitonin gene-related peptide, neuropeptide Y, endothelin-1 and corticotropin-releasing hormone were also detected in the tumor tissues. The tumor tissue concentrations of immunoreactive adrenomedullin were comparable to those of these four peptides, but much lower than those of ACTH. Northern blot analysis showed the expression of adrenomedullin mRNA in one tumor from which sufficient tissue was available for such study. The plasma concentration of immunoreactive adrenomedullin was increased in one patient (41.3 pmol/l, control 13.5 +/- 3.6 pmol/l, mean +/- S.D., n = 12).. These results suggest that adrenomedullin is produced by ectopic ACTH-secreting tumors, together with other neuropeptides, and raise the possibility that adrenomedullin is related to the pathophysiology of these tumors.

Topics: Adrenocorticotropic Hormone; Adrenomedullin; Adult; Bronchial Neoplasms; Carcinoid Tumor; Female; Humans; Male; Middle Aged; Neuroendocrine Tumors; Peptides; RNA, Messenger; Thymus Neoplasms

Adrenomedullin (AM) is a potent hypotensive peptide recently discovered in extracts of human pheochromocytoma. In this report we present evidence, using reverse transcriptase-polymerase chain reaction, immunocytochemistry, and in situ reverse transcriptase-polymerase chain reaction, that AM is synthesized by several cell populations of the normal lung, tumor cell lines of pulmonary origin, and tumor specimens. Among the normal cell populations of the lung, we found AM expression in the columnar epithelium, some glands, neurons of the pulmonary parasympathetic nervous system, endothelial cells, chondrocytes, alveolar macrophages, and smooth muscle cells. In tumors, AM expression was located in most of the nonsmall cell lung carcinomas and in half of the small cell lung carcinomas studied. These findings suggest that AM may play a broad role in respiratory homeostasis and lung carcinogenesis.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Adrenomedullin; Amino Acid Sequence; Base Sequence; Blotting, Southern; Blotting, Western; Carcinoid Tumor; Carcinoma, Small Cell; DNA, Antisense; Epithelial Cells; Epithelium; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Lung; Lung Neoplasms; Macrophages; Molecular Sequence Data; Muscle, Smooth; Oligonucleotides; Peptides; Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured