Studies on the biological characterization and mitogenic interactions between hepatic stimulator substance and acidic fibroblast growth factor.

During liver regeneration, hepatic stimulator substance (HSS) and acidic fibroblast growth factor (FGF-1) are produced in the liver. These growth factors may be involved in liver growth control but an understanding of their regulatory interactions is limited. To further characterize the mitogenic activity of HSS, we compared its effects with FGF-1 in cells of hepatocyte, non-parenchymal liver epithelial and non-hepatic lineages. Our studies with these cell types demonstrated differences in the mitogenic specificities of HSS and FGF-1. Whereas exposure of primary hepatocytes to epidermal growth factor and HSS synergistically increased DNA synthesis, simultaneous exposure to HSS and FGF-1 resulted in no such effect. Receptor-binding assays showed that HSS did not compete with FGF-1 in binding to FGF-1 receptors on rat primary hepatocytes. Additional immunoblot analysis demonstrated no cross-reactivity between FGF-1 antibodies and HSS. Distinct mitogenic and immunologic properties of HSS and FGF-1 should facilitate further analysis of liver regeneration and hepatic oncogenesis.