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Submitted on June 25, 2003
Accepted on November 21, 2003
mRNA is dependent on the biological clock in the suprachiasmatic nucleus (SCN), while that of TR
1 mRNA is modified by food intake
1 Department of Endocrinology & Metabolism. Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.; From the Department of Hypothalamic Integration Mechanisms, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ, Amsterdam, The Netherlands.
* To whom correspondence should be addressed. E-mail: o.bakker{at}amc.uva.nl.
Previous studies have shown a diurnal variation of certain isoforms of thyroid hormone receptors (TR) in rat liver. The genesis of these diurnal changes is still unknown. To clarify whether the biological clock, located in the hypothalamic suprachiasmatic nucleus (SCN), is involved we made selective SCN lesions. Rats with an SCN lesion lost their circadian rhythm of plasma corticosterone and TSH when compared with intact animals. TR
1 and TR2 mRNA expression of control rats was higher in the light period than in the dark period; changes that were abolished in the SCNx rats. In contrast, liver TR
1 mRNA of intact rats showed a diurnal variation that failed to reach statistical significance. To evaluate whether these effects could be explained indirectly by the disappearance of rhythmic feeding behavior in rats with SCN lesions, we performed a second experiment in which otherwise intact animals were subjected to a regular feeding schedule, with one meal every 4 h. When compared with rats with free access to food, regular feeding only affected TR1 mRNA expression but had no effect on the diurnal changes in TR1 and TR2.
We conclude that liver TR1 expression is most clearly affected by food intake. Diurnal changes in liver TR1 and TR2 are controlled by the biological clock in the SCN, but not via changes in the daily rhythm of food intake. The findings may have physiological relevance for diurnal variation of T3-dependent gene expression which is supported by a diurnal variation in the expression of the 5'-deiodinase gene.
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