Age-related changes in DNA synthesis stimulated by epinephrine and isoproterenol in primary cultured rat hepatocytes.

We examined epinephrine- and isoproterenol-stimulated DNA synthesis in primary cultured hepatocytes from 6-, 12-, and 24-month-old rats. Epinephrine-stimulated DNA synthesis in 6-month-old rat hepatocytes began after 20 h and reached a maximum at 50 h. Similarly, isoproterenol-stimulated DNA synthesis in 6-month-old rat hepatocytes began after 10 h and reached a maximum at 45 h. In contrast, both epinephrine- and isoproterenol-stimulated DNA synthesis in 12- and 24-month-old rat hepatocytes were reduced approximately 40-60% and 80%, respectively, as compared to that at 6 months. Both epinephrine- and isoproterenol-stimulated DNA synthesis were strongly inhibited by the beta-adrenergic antagonist, propranolol, but not by the alpha 1-adrenergic antagonist, prazosin, or the alpha 2-adrenergic antagonist, yohimbine. However, in the presence of EGF, epinephrine-stimulated DNA synthesis activity was inhibited by prazosin but not by propranolol. These results indicate that stimulated DNA synthesis in rat hepatocytes declines with age and that there are two different pathways for epinephrine-stimulated DNA synthesis in the presence or absence of EGF.