DISTRIBUTION OF EPIDERMAL GROWTH-FACTOR BINDING-SITES IN THE ADULT-RAT LIVER

The localization of epidermal growth factor (EGF) receptors was studied in the liver by use of light microscope autoradiography performed at different time intervals (2-60 min) after intravenous injection of 125I-EGF into adult rat. The results revealed a substantial binding of EGF to parenchymal cells of the liver. Control experiments indicated that the autoradiographic labeling was due to specific interaction of 125I-EGF with its receptor. A very steep portal-to-central lobular concentration gradient for 125I-EGF uptake was observed. The time course study performed on parenchymal cells of periportal regions of lobules showed that, at the 2-min time interval, most silver grains were found at the periphery of these cells and that the maximal values were reached 7 min after injection. After, the number of grains decreased progressively and their localization in the cytoplasm indicated the internalization of the ligand. The present results demonstrate that EGF injected into the general circulation preferentially binds to hepatocytes located in the periportal area and is rapidly internalized.