The effect of concentration on hepatic transport of exogenous epidermal growth factor

Epidermal growth factor (EGF), taken up by rat liver hepatocytes, is primarily transported to the lysosomes and degraded. However, a small but significant percentage of endocytosed EGF is transported by a nonlysosomal pathway and is secreted intact into bile. There is no information as to the mechanisms that regulate the selection of transport pathway and thereby determine the different metabolic fates for EGF. The experiments reported here were undertaken to determine whether the amount of exogenous EGF administered to the liver (the transport load) might affect the selection of the transport pathway. If "excess" EGF, exceeding some as yet undetermined threshold, is preferentially transported by the lysosomal pathway, then the proportion of degraded EGF secreted into bile should increase as a function of the amount of EGF administered. 125I-EGF (3 to 175 ng) was injected into rat portal veins, and bile samples were collected via cannula. The radioactivity secreted into bile was measured, and the bile samples were immunoprecipitated with anti-EGF antiserum. The proportion of intact vs. degraded EGF in bile was determined by the percentage of immunoprecipitable radioactivity. Regardless of the amount of EGF injected, the pattern of its secretion was unaltered. The percentage of immunoprecipitable EGF in bile was the same for all doses. Therefore, the amount of EGF that was degraded did not change as a function of EGF concentration, implying that the lysosomal pathway was not preferentially utilized as the transport load increased. In conclusion, transport load does not appear to be a regulatory mechanism in the selection of transport pathway utilized by EGF.