Hormonal activation of glycogen phosphorylase in hepatocytes from hypothyroid rats.

The ability of catecholamines and glucagon to stimulate glycogen phosphorylase activity was examined in hepatocytes isolated from euthyroid and hypothyroid fed female rats. Hypothyroidism did not alter the ability of either phenylephrine or epinephrine to activate glycogen phosphorylase. Activation of glycogen phosphorylase in response to a maximal concentration of isoproterenol, however, was 100% higher in hepatocytes isolated from hypothyroid as compared to euthyroid rats. In the presence of 50 ~FLM methylisobutyl xanthine hypothyroid rat hepatocytes displayed half-maximal activation of phosphorylase with only 111~ isoproterenol, whereas euthyroid rat hepatocytes required 33 11~ isoproterenol for half-maximal activation. Methylisobutyl xanthine (50 PM) potentiated the ability of isoproterenol but not that of epinephrine or phenylephrine, to activate phosphorylase in euthyroid rat hepatocytes while potentiating the activation of phosphorylase in response to isoproterenol and to epinephrine in hypothyroid rat hepatocytes. Glucagon activation of glycogen phosphorylase in rat hepatocytes was not altered by hypothyroidism in either the presence or absence of methylisobutyl xanthine. Cyclic AMP accumulation following epinephrine or isoproterenol stimulation was dramatically higher in hypothyroid as compared to euthyroid rat hepatocytes, in both the absence or presence of 50 PM methylisobutyl xanthine. Glucagon stimulation of cyclic AMP accumulation was not altered by hypothyroidism. The amplified cyclic AMP accumulation and phosphorylase activation of hypothyroid rat hepatocytes in response to isoproterenol could be blocked by propranolol (10 PM) but not phentolamine (10 PM). Hypothyroidism appears to selectively enhance activation of glycogen phosphorylase and stimulation of cyclic AMP accumulation by P-adrenergic agonists in isolated rat hepatocytes. Thyroid hormones appear to have the opposite effect on fl-adrenergic responses in the liver as compared to heart and adipose tissue.