Production and secretion of two vasoactive peptides, adrenomedullin and endothelin-1, by cultured human adrenocortical carcinoma cells

The production and secretion of peptides by adrenocortical tumors have not been well studied. We therefore studied the production and secretion of two vasoactive peptides, adrenomedullin and endothelin-1 in SW-13 human adreno cortical carcinoma cells by radioimmunoassay and Northern blot analysis. Bo th immunoreactive-adrenomedullin and immunoreactive-endothelin were detecte d in the culture medium of SW-13 cells (27.7 +/- 1.6 fmol/10(5) cells/24 h and 11.0 +/- 0.8 fmol/10(5) cells/24 h, respectively, mean +/- SEM, n = 6). Northern blot analysis showed the expression of adrenomedullin mRNA and en dothelin-1 mRNA in SW-13 cells. On the other hand, no significant amount of calcitonin gene-related peptide, corticotropin-releasing hormone, neuropep tide Y, or urocortin was secreted by SW-13 cells. Treatment with ACTH (10(- 9)-10(-7) mol/l), angiotensin II (10(-9)-10(-7) mol/l), or dexamethasone (1 0(-8)-10(-6) mol/l) for 24 h had no significant effects on immunoreactive-a drenomedullin levels and immunoreactive-endothelin levels in the culture me dium of SW-13. Treatment with tumor necrosis factor (TNF)-alpha (20 ng/ml) increased significantly both immunoreactive-adrenomedullin levels and immun oreactive-endothelin levels in the culture medium. Interferon-gamma (100 U/ ml) increased the immunoreactive-endothelin levels, but not immunoreactive- adrenomedullin levels, whereas interleukin-1 (IL-1)beta (10 ng/ml) increase d immunoreactive-adrenomedullin levels, but not immunoreactive-endothelin l evels. These findings indicate that SW-13 human adrenocortical carcinoma ce lls produce and secrete two vasoactive peptides, adrenomedullin, and endoth elin-1 and that the secretion of these two peptides is modulated differentl y by cytokines. (C) 2000 Elsevier Science Inc. All rights reserved.