SOMATOSTATIN ANALOG INDUCES INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-1 (IGFBP-1) EXPRESSION IN HUMAN HEPATOMA-CELLS

As the somatostatin analog octreotide suppresses pituitary GH secretion and circulating IGF-1 levels, we examined its effects on human hepatoma (hep G2) cells which selectively express IGFBP-1. octreotide (60 nM) stimulated IGFBP-1 up to 4.1-fold (p<0.001 after 24 hrs). Induction of IGFBP-1 was first detectable after 12 hrs of 6 nM octreotide (1.5-fold, p<0.03), and was confirmed by ligand blotting. Cholera toxin and forskolin induced IGFBP-1 independently and were also additive with octreotide. IGFBP-1 mRNA expression was induced 2.7-fold by octreotide. Thus, octreotide induces basal and stimulated IGFBP-1 in hepatocytes independently of insulin and GH. As IGFBP-1 may regulate peripheral IGF-1 action, induction of IGFBP-1 represents a novel pituitary-independent mechanism for octreotide action.