Differential responsiveness of cultured suckling and adult rat hepatocytes to growth-promoting factors: entry into S phase and mitosis.

The capacity of suckling and adult rat hepatocytes in culture to enter into S phase and mitosis in response to EGF, insulin, and glucagon was measured. Both cell types were isolated in high yield and purity and cultured in the absence of serum under identical conditions. At the time of isolation, suckling rat hepatocytes were all diploid and in the G1 phase of the cell cycle. Adult rat hepatocytes constituted a population of mixed ploidy level, as shown by flow cytometry. Upon stimulation, both suckling and adult rate hepatocytes entered S phase after a minimum lag period of 24 h. For suckling rat hepatocytes EGF was required, but its stimulating action was dependent on insulin and/or glucagon. In contrast, adult rat hepatocytes entered into S phase in response to EGF alone; insulin and glucagon did not significantly potentiate its effect. Under optimal hormonal stimulation for entry into S phase a large proportion of suckling rat hepatocytes underwent mitosis, whereas only a few mitoses were observed in the case of adult rat hepatocytes. Therefore, there is a differential response of suckling and adult rat hepatocytes to growth factors which correlates with ploidy level, and this difference may be associated with the degree of maturation.