Rapid synergistic interaction between thyroid hormone and carbohydrate on mRNAS14 induction.

Recent studies have shown that hepatic mRNAS14 responds rapidly to thyroid hormone administration. Moreover, this mRNA is known to increase in mass with the administration of a high carbohydrate fat-free diet. Therefore, it appears to share many of the same properties of the known hepatic lipogenic enzymes. Because the lipogenic enzymes display a synergistic interaction between thyroid hormones and carbohydrates, we investigated the kinetics of response of mRNAS14 to carbohydrate feeding, as well as its interaction with triiodothyronine (T3). We found that mRNAS14 responds rapidly to the dietary administration of sucrose in euthyroid rats, with a 2-fold increase within 30 min, and a 25-fold increase by 4 h. On the other hand, when given to hypothyroid rats, sucrose ultimately lead to only a 2-3-fold increase in the level of mRNAS14, attaining a level less than that found in starved euthyroid rats. The diminished response of mRNAS14 to sucrose in hypothyroidism could not be enhanced by insulin administration. However, administration of replacement doses of T3 (400 ng/100 g of body weight) immediately restored the rapid response to sucrose feeding. The response of sucrose and T3 was synergistic. Dose-response studies with T3 indicated that the rapid interaction between T3 and sucrose was limited by the occupancy of the T3 nuclear receptor. A similar synergistic response to T3 and glucose was noted in primary hepatocyte cultures, thus indicating that the synergism between these two stimuli is not due to changes in extrahepatic hormones or metabolites. Our data are most consistent with the hypothesis that the T3-nuclear receptor complex multiplies a signal generated by carbohydrate metabolism to induce hepatic mRNAS14. The interaction does not appear to require the preliminary induction of carbohydrate-metabolizing enzymes and their mRNAs.