Nuclear 3,5,3′-Triiodothyronine Receptor Occupancy, Phosphoenolpyruvate Carboxykinase (PEPck) Messenger Ribonucleic Acid Levels and PEPck Enzyme Activity in Rat Liver*

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Abstract
The expression of the gene coding for phosphoenolpyruvate carboxykinase (PEPck) is under complex multihormonal control. A stimulatory effect of T3 on the expression of this gene has been described, but it has not been related to nuclear T3 receptor occupancy. We therefore studied simultaneously nuclear T3 receptor occupancy, PEPck enzyme activities, and PEPck messenger RNA (mRNA) levels in the liver of thyroidectomized, T3-treated rats. A dose-dependent increase in receptor occupancy and in enzyme activities was observed 24 h after a single ip injection of T3. However, no increase in the levels of PEPck mRNA was observed, using a specific complementary DNA (pPCK10). To evaluate this further, time-course experiments were performed over a 24 h period after a single ip injection of a receptor saturating dose of T3. These experiments showed simultaneous increases of PEPck enzyme activities and PEPck mRNA levels. Receptor occupancy had increased to 95% 3 h after injection of T3, whereas maximal levels of enzyme activity and mRNA were obtained 6-12 h after T3 administration. Translational efficiency did not change during induction. Twenty-four hours after T3 administration , mRNA levels and enzyme activity had declined, but receptor occupancy was still maximal. We conclude that T3 influences PEPck gene expression primarily at a pretranslational (transcriptional) level. The transient increase in PEPck mRNA despite persisting full receptor occupancy suggests a modification in time of the interaction between the T3-receptor complex and the regulatory region of the PEPck gene.

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