Effects of EGF and calcium on adult parenchymal hepatocyte proliferation

Adult rat hepatocytes were grown in serum-free medium containing 0.05-4 mM Ca++ and 40 ng/ml EGF. After 48 hours of cultivation the mitotic index and the percentage of second division metaphases were determined. The results demonstrated a maximum proliferation response to EGF at a Ca++ concentration of 0.4 mM. With lower and higher external Ca++ concentrations the fraction of cells undergoing more than one cell division decreased. At lower Ca++ concentrations this decrease appears to result from a reduced viability. In contrast, the low response to EGF at higher Ca++ concentrations--especially in the physiological range--may reflect the influence of Ca++ on the state of hepatocyte differentiation.