Zonal differences in effects of HGF/SF and EGF on DNA synthesis in hepatocytes under fed or starved conditions

Zonal differences of DNA synthesis in hepatocytes induced by hepatocyte gro wth factor and/or scatter factor (HGF/SF) and epidermal growth factor (EGF) were investigated using male Wistar rats under fed or starved conditions. Overall, DNA synthesis was greater in fed rats than in starved rats. The pr edominance of EGF in periportal hepatocytes (PPH) on zonal DNA synthesis wa s reversed by starved conditions, but the predominance of HGF/SF on zonal D NA synthesis in perivenous hepatocytes (PVH) was not influenced by nutritio nal conditions. I-125-labeled EGF and I-125-labeled HGF/SF-receptor binding studies revealed no significant difference between PPH and PVH in starved or fed rats. To investigate the mechanism of the signal transduction pathwa y, we used genistein, an inhibitor of tyrosine kinase. Genistein had differ ent effects on zonal difference in EGF and HGF/SF. In EGF, 1 mu g/ml genist ein abolished zonal differences, but in HGF/SF 1 mu g/ml genistein did not abolish zonal differences. These data suggest that, in contrast to HGF/SF, zonal difference of DNA synthesis by EGF was dependent on nutritional condi tions and DNA synthesis induced by HGF/SF and EGF might be related to tyros ine kinase, but the influence of tyrosine kinase on DNA. synthesis was diff erent between HGF/SF and EGF.