Effects of EGF and calcium on adult parenchymal hepatocyte proliferation

Abstract

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.