PRODUCTION AND SECRETION OF ADRENOMEDULLIN BY CULTURED CHOROID-PLEXUSCARCINOMA-CELLS

Adrenomedullin is a potent vasodilator peptide that was originally iso lated from pheochromocytoma. The production and secretion of adrenomed ullin by cultured choroid plexus carcinoma cells were studied by radio immunoassay and northern blot hybridization. Choroid plexus carcinoma is a rare malignant tumor derived from the epithelium of the choroid p lexus. Immunoreactive adrenomedullin was detected in the conditioned m edium of choroid plexus carcinoma cells (40.8 +/- 7.5 fmol/10(5) cells /24 h; mean +/- SEM, n = 5). Reverse-phase HPLC of the conditioned med ium showed one major peak of the immunoreactive peptide eluting in the position of synthetic human adrenomedullin and two smaller peaks elut ing earlier. Addition of interleukin-1 beta (10 ng/ml) alone or in com bination with three cytokines, interferon-gamma (100 U/ml), tumor necr osis factor-alpha (20 ng/ml), and interleukin-1 beta (10 ng/ml), cause d significant increases in the immunoreactive adrenomedullin concentra tions in the medium (similar to 175 and 293% of the control level, res pectively). Northern blot analysis showed the expression of 1.6-kb adr enomedullin mRNA in the total RNA sample prepared from cultured choroi d plexus carcinoma cells. Treatment with either interleukin-1 beta or the combination of three cytokines caused significant increases in lev els of adrenomedullin mRNA in parallel with those in immunoreactive ad renomedullin concentrations in the conditioned medium. These findings raise a possibility that adrenomedullin is secreted from the choroid p lexus and has physiological roles in the CNS via the CSF. In addition, adrenomedullin secreted from choroid plexus carcinoma may be related to the pathophysiology of the tumor.