Inhibition of rat hepatocyte multiplication by serum factors. Physiological significance.

A serum factor that inhibits the passage of hepatocytes from the G1 to the S phase and another that induces the production of binucleate hepatocytes were studied at different growth stages in the rat and under conditions inducing hepatocyte multiplication: partial hepatectomy and injection of irritants. A close relationship was found between the presence of these serum factors and the patterns of hepatocyte multiplication. When many S phase hepatocytes and few binucleate cells are produced in the liver, as in the first three weeks of life or after partial hepatectomy in adults, the mitotic inhibition and binucleate cell production activities are not found in the sera. Conversely, when the number of S phase hepatocytes decreases progressively and many binucleate cells are produced, as in weanling and adult rats or in baby rats during the late period after an irritating injection, these activities are present in the sera. These facts support the hypothesis that these factors play a role in the physiological regulatory mechanism of liver growth.