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J. Biol. Chem., Vol. 261, Issue 21, 9583-9586, Jul, 1986
CN Mariash, S Seelig, HL Schwartz and JH Oppenheimer
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.
Rapid synergistic interaction between thyroid hormone and carbohydrate on mRNAS14 induction
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