Role of Cyclic Adenosine 3',5'-Monophosphate in the Induction of Hepatic Enzymes

Abstract

The induction of tyrosine aminotransferase in H-4-11-E hepatoma cells (a strain derived from H-35 Reuber hepatoma) in the presence of dibutyryl cyclic adenosine 3',5'-monophosphate (cyclic AMP) requires low concentrations of hydrocortisone. Incubation of the cells with 10-4 m dibutyryl cyclic AMP alone failed to induce the enzyme. Hydrocortisone must be continuously present for the induction of tyrosine aminotransferase in the presence of dibutyryl cyclic AMP. The induction of tyrosine aminotransferase by 10-8 m hydrocortisone plus 10-4 m dibutyryl cyclic AMP requires both protein and RNA synthesis. Glucagon (free of insulin) alone or with hydrocortisone neither increases the adenyl cyclase activity nor induces tyrosine aminotransferase in H-4-11-E hepatoma cells. Hydrocortisone has no effect on the uptake of exogenous dibutyryl cyclic AMP and, conversely, dibutyryl cyclic AMP has no effect on the uptake of hydrocortisone. That hydrocortisone might increase the cyclic AMP-binding activity of soluble proteins has also been excluded. Hydrocortisone increases both the total activity of protein phosphokinase (or phosphokinases) of the cells and the phosphorylation in vivo of nuclear histones.