Effect of hypothyroidism and thyroid hormone replacement on the level of protein kinase C and protein kinase A in rat liver.

We investigated the influence of the thyroid hormone status on the levels of protein kinases C (PKC) and A (PKA) in the soluble fraction of rat liver. The immunodetectable PKC level in hypothyroid liver was elevated 7.7-fold, whereas the phorbol-ester binding capacity and the immunodetectable alpha-PKC level were increased 2.4- and 2.6-fold, respectively. Conversely, in hypothyroid livers the abundance of the regulatory type I and the catalytic subunits of PKA were lowered to 42% of the euthyroid level as determined by immunoblotting and by measuring the substrate specific phosphorylation rate of PKA. These changes in the PKC and PKA levels were reversible upon treatment with 0.5 microgram T4/100 g body weight for 2-21 days. The thyroid state dependent alterations in hepatic PKC and PKA levels may be responsible for the known changes in the response of hepatocytes to other hormonal stimuli in hypothyroidism.