Cooperative effect of thyroid and glucocorticoid hormones on the induction of hepatic phospho enol pyruvate carboxykinase in vivo and in cultured hepatocytes

The present study investigates the effect and interaction of glucocorticoid and thyroid hormones on the induction of phospho enol pyruvate carboxykinase (PEPck) mRNA and enzyme protein under in vivo conditions and in serum‐free cultured hepatocytes from hypothyroid rats. In hypothyroid/adrenalectomized rats T3 significantly enhanced the cAMP induced PEPck mRNA activity within 3—6 h. This effect was further enhanced by the presence of glucocorticoids. The half‐life of PEPck mRNA, as determined after administration of cordycepin, was not affected by hypothyroidism or hyperthyroidism ( t 1/2 ∼ 45 min), but considerably prolonged by the absence of glucocorticoid hormones ( t 1/2 < 80 min). In hepatocytes in culture Bt 2 cAMP (0.2 mM) provoked an increase in translatable PEPck mRNA within 2 h incubation time. Preincubation with either T3 (0.1 μM) or dexamethasone (0.1 μM) for 4 h significantly enhanced the cAMP response on PEPck mRNA. Addition of both, T3 plus dexamethasone further enhanced this Bt 2 cAMP‐mediated effect. By measurement of PEPck synthesis corresponding findings were observed. It is concluded that glucocorticoid and thyroid hormones predominantly enhance the cAMP‐provoked induction of hepatic PEPck mRNA and, consequently, of PEPck synthesis. Their effect is rapid, significant and additive, indicating an independent action. While glucocorticoids, in addition, accelerate PEPck mRNA degradation, the PEPck mRNA decay rate is similar in the presence and absence of thyroid hormones.