synergistic influence of epidermal growth factor insulin and transferrin on human fetal kidney in culture in human fetal kidneys 1521 weeks of gestation maintained in serumfree organ culture protein synthesis remained relatively constant but dna synthesis decreased dramatically after 2 days the addition of transferrin alone had no influence but insulin and epidermal growth factor egf both significantly stimulated dna and protein synthesis when supplemented in combination transferrin strongly potentiated the insulin effect and after 5 days of culture dna synthesis was practically restored to values observed in control uncultured renal explants day 0 when egf a potent mitogen was added as a third factor the stimulating effectiveness of the insulin plus transferrin combination was significantly reduced however egf had no such inhibiting influence on protein synthesis differentiation of brush border membranes as evaluated by hydrolase activities was not importantly induced nor retarded by any of the three factors supplemented either alone or in combination the present results indicate that the individual effects of the three factors are not additive but suggest that they rather act synergistically through a complex mechanism of receptor crosstalk in our laboratory there is convincing indication that the response of fetal organs varies according to age proliferative state of tissues as well as stage of differentiation