Inhibition of rat hepatocyte multiplication by serum and liver factors: physiological development and experimental induction.

Inhibition of the G1-S transition in synchronized baby rat hepatocytes was obtained by a subcutaneous injection of adult rat liver cytosol. This inhibitory activity was observed only with liver cytosol and not with kidney or spleen cytosol. The liver cell was a relatively specific target: no modifications were recorded in the kidney or submaxillary gland and inconsistant variations were found with tongue epithelium. The activity was associated with a non-dialysable factor. Physiological investigations support the opinion that the liver factor is the origin of the serum factor which had previously been described. Both factors were absent during the first three weeks of life. They appeared together during the 4th week in correlation with a decreasing rate of liver cell multiplication and then reached progressively their definitive adult levels. After 2/3 hepatectomy in adults, the liver cytosol retained its inhibitory activity, but the serum factor was reversibly neutralized by an antagonistic factor. Both inhibitory factors could be prematurely induced in baby rats and appeared transiently during the period of low mitotic activity following a wave of synchronized liver cells generated by an irritating stress. This inhibitory system is characteristic of the last developmental stages of the liver when growth decelerates before reaching a steady state. It seems to reduce the multiplication of hepatocytes by decreasing their sensitivity to stimuli initiating cell replication.