Functional control of hepatocyte proliferation. Comparison with the temporal control of cardiomyocyte proliferation

A 4.1-fold difference in liver weight, a 2.5 fold difference in hepatocyte number, and a 1.5-fold difference in mean ploidy were seen in mice on the day of weaning (day 21) reared four (fast-growing group) or sixteen (slow-growing group) to a litter. These differences in proliferation parameters were eliminated in adult mice that had similar liver weights. The kinetics of the changes were not time dependent, i.e. under temporal control, but corresponded to liver-weight kinetics. The definitive number of hepatocytes was established by 3 weeks of age in the fast-growing mice and by 3 months in the slow-growing ones. In contrast to the hepatocytes, multiplication of heart myocytes of the same mice was inhibited by 3-4 days after birth and polyploidization ceased about 3 weeks after birth in mice from both fast- and slow-growing litters, and a stable (approximately 40%) difference in cardiac myocyte number and ploidy persisted throughout the entire period of ontogenesis. It is concluded that hepatocyte proliferation is under functional control whereas cardiac myocyte proliferation is time dependent. Postmitotic hypertrophy of the cell cytoplasm is functionally dependent in both heart and liver. In slow-growing mice, an increase in heart weight occurs only as a result of cytoplasmic hypertrophy, whereas in the liver, cell number and ploidy are both involved.