Activation of glycogenolysis in neonatal liver.

The initial activation of hepatic glycogenolysis in the neonate was studied in the guinea pig. The glycogen content (58 to 70 mg/g of tissue) in liver of newborn animals remained unchanged for at least 3 h, and dropped rapidly between 4 and 6 h after birth to minimal values of 14 to 20 mg/g at 12 h. The activity of glycogen synthase a decreased by 28% to minimal values within 2 h without any change in total synthase activity. The activity of phosphorylase a increased 22 to 53% within 2 to 4 h. Both the phosphorylase activity ratio (AMP/+ AMP) and the ratio of phosphorylase a to synthase a increased markedly during this period, attaining maximal values at 4 h, which coincided with the onset of glycogen mobilization. Glucagon administration to 1-h-old newborn animals induced only a 20% decrease in liver glycogen. In older animals the decrease was much more pronounced. The age-dependent response to glucagon could be duplicated in isolated hepatocytes. In this system the glycogenolytic effect of glucagon was less than 10% in cells prepared from animals aged 0 to 3 h. Thereafter, the effect was progressively increased and was sensitive to p-adrenergic blockade. A similar age-dependent response was observed with the p-agonist, isoproterenol, and with the mixed agonist epinephrine. In contrast, dibutyryl CAMP-induced glycogenolysis in these hepatocytes was independent of age of the donor animals, indicating that the response to p-adrenergic agonists is determined by age-dependent changes in the receptor system for these hormones. These results show that there is a delay in the initial mobilization of hepatic glycogen in the newborn and that factors which determine the precise programming of this process are related to the development of hepatic sensitivity to hormones which interact with adrenergic systems regulating carbohydrate metabolism.