ALTERATION OF SECRETION OF PARATHYROID HORMONE-RELATED PEPTIDE AND EXPRESSION OF ITS MESSENGER-RNA IN A HUMAN HEPATOMA-CELL LINE (HEP G2) TREATED WITH AGENTS THAT AFFECT CELL-GROWTH

Previously, using human hepatoma cells (Hep G2), we found that immunon eutralization of secreted PTHrP increased cell growth. Here we asked w hether PTHrP production was affected by agents that alter growth of He p G2 cells. Immunoreactive PTHrP in medium and PTHrP mRNA expression w ere examined. Treatment of cells with 10 mu M hydrocortisone or 1 ng/m L TGF-beta 1 for 72 h inhibited cell growth by 28 +/- 6 and 36 +/- 2% and increased PTHrP in medium by 128 +/- 10 and 525 +/- 27%, respectiv ely. The increase in PTHrP produced. by both agents was dose- and time -dependent, and the increased PTHrP was accompanied by dose- and time- dependent enhanced expression of PTHrP mRNA. In contrast, 10% fetal bo vine serum (FBS) for 72 h increased cell growth by 38 +/- 6% (vs serum -free medium) and decreased PTHrP production by 49 +/- 4% whereas cult ure in high glucose (3-4g/L) increased cell growth by 43 +/- 1% (vs 1 g/L glucose) and decreased PTHrP by 55 +/- 0.4%. Inhibition of PTHrP b y both FBS and glucose was dose-dependent; FBS also inhibited PTHrP mR NA. The results show that increased cell growth was associated with de creased PTHrP production, while decreased growth was accompanied by in creased PTHrP production. The findings imply that PTHrP may help media te growth effects of these agents on Hep G2 cells.