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
adrenocortical carcinoma cells by radioimmunoassay and Northern blot analysis. Both immunoreactive-
adrenomedullin and immunoreactive-
endothelin were detected 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
endothelin-1 mRNA in SW-13 cells. On the other hand, no significant amount of
calcitonin gene-related peptide,
corticotropin-releasing hormone,
neuropeptide 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 (10(-8)-10(-6) mol/l) for 24 h had no significant effects on immunoreactive-
adrenomedullin levels and immunoreactive-
endothelin levels in the culture medium of SW-13. Treatment with
tumor necrosis factor (
TNF)-alpha (20 ng/ml) increased significantly both immunoreactive-
adrenomedullin levels and immunoreactive-
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) increased immunoreactive-
adrenomedullin levels, but not immunoreactive-
endothelin levels. These findings indicate that SW-13 human
adrenocortical carcinoma cells produce and secrete two vasoactive
peptides,
adrenomedullin, and
endothelin-1 and that the secretion of these two
peptides is modulated differently by
cytokines.