Effects of epidermal growth factor/urogastrone and associated pancreatic hormones on mitotic cycle phases and proliferation kinetics of neonatal rat hepatocytes in primary culture

Low doses (10(-14)--10(-11) M) of epidermal growth factor (EGF)/urogastrone and/or equimolar mixtures of glucagon and insulin administered to 4-day-old primary neonatal rat liver cultures stimulated both DNA synthesis and proliferation of hepatocytes within 24 h. The precise roles played in this process by EGF and the two pancreatic hormones were investigated by constructing curves of the fraction of labeled hepatocytes in mitosis and studying the dilution of incorporated [3H]thymidine with time. The results indicate that EGF both activates and then promotes prereplicative development of hepatocytes, while glucagon and insulin only promote prereplicative development.