Expression of adrenomedullin mRNA in adrenocortical tumors and secretion of adrenomedullin by cultured adrenocortical carcinoma cells

Immunoreactive-adrenomedullin concentrations and the expression of adrenome dullin mRNA were studied in the tumor tissues of adrenocortical tumors. Nor thern blot analysis showed the expression of adrenomedullin mRNA in tumor t issues of adrenocortical tumors, including aldosterone-producing adenomas, cortisol-producing adenomas, a non-functioning adenoma and adrenocortical c arcinomas, as well as normal parts of adrenal glands and pheochromocytomas. On the other hand, immunoreactive-adrenomedullin was not detected in about 90% cases of adrenocortical tumors (<0.12 pmol/g wet weight (ww)). Immunor eactive-adrenomedullin concentrations ranged from 0.44 to 198.2 pmol/g ww i n tumor tissues of pheochromocytomas and were 9.2 +/- 1.2 pmol/g ww (mean /- SD, n = 4) in normal parts of adrenal glands. Adrenomedullin mRNA was ex pressed in an adrenocortical adenocarcinoma cell line, SW-13 and immunoreac tive-adrenomedullin was detected in the culture medium of SW-13 (48.9 +/- 1 .8 fmol/10(5) cells/24 h, mean +/- SEM, n = 4). On the other hand, immunore active-adrenomedullin was not detectable in the extract of SW-13 cells (<0. 09 fmol/10(5) cells), suggesting that adrenomedullin was actively secreted from SW-13 cells without long-term storage. These findings indicate that ad renomedullin is produced and secreted, not only by pheochromocytomas, but a lso by adrenocortical tumors. Undetectable or low levels of immunoreactive- adrenomedullin in the tumor tissues of adrenocortical tumors may be due to Very rapid secretion of this peptide soon after the translation from these tumors. (C) 1998 Elsevier Science Inc.