Glucocorticoid‐Dependent Induction of mRNA Coding for Phosphoenolpyruvate Carboxykinase (GTP) in Rat Kidney

Abstract

The glucocorticoids induce the synthesis of phosphoenolpyruvate carboxykinase (GTP) in rat kidney as a consequence of an increase in the level of the specific enzyme mRNA. The mRNA induction was characterized with respect to its time course after hormone administration and its sensitivity to cycloheximide. The level of rat kidney mRNA directing the synthesis of phosphoenolpyruvate carboxykinase in a wheat germ translation system nearly doubled within 2 h of a dexamethasone injection and further increased to 4 times the initial value at 6 h of treatment and to 5 times at 10 h. Cycloheximide injected 30 min prior to dexamethasone prevented the mRNA increase. When injected 5 h after dexamethasone, the inhibitor of protein synthesis blocked the rise of phosphoenolpyruvate carboxykinase mRNA occurring normally between 5 and 10 h after treatment with dexamethasone. Maximal inhibition of protein synthesis on the one hand and of mRNA induction on the other were achieved at the same dose of cycloheximide, suggesting that the 2 effects might be related. Dexamethasone caused an increase in the functional level of several as yet unidentified mRNA and that coding for phosphoenolpyruvate carboxykinase. The main points emerging from this study are the virtual absence of lag between dexamethasone administration and increase in phosphoenolpyruvate carboxykinase mRNA; the inhibition of phosphoenolpyruvate carboxykinase mRNA induction by cycloheximide, suggesting a possible requirement for ongoing protein synthesis and the existence in the kidney of a glucocorticoid-responsive domain comprising several distinct proteins.