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Diurnal Variation in Rat Liver Thyroid Hormone Receptor (TR)- Messenger Ribonucleic Acid (mRNA) Is Dependent on the Biological Clock in the Suprachiasmatic Nucleus, whereas Diurnal Variation of TRß1 mRNA Is Modified by Food Intake

Department of Endocrinology and Metabolism (B.Z.D., M.P.-T.S., E.F., O.B., W.M.W.), Academic Medical Center, University of Amsterdam, and Department of Hypothalamic Integration Mechanisms (A.K.), Netherlands Institute for Brain Research, 1105 AZ Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: O. Bakker, Department of Endocrinology and Metabolism, F5-171, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. 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. TR1 and TR2 mRNA expression of control rats was higher in the light period than in the dark period; changes that were abolished in the rats with SCN lesions. In contrast, liver TRß1 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 (RF) schedule, with one meal every 4 h. When compared with rats with free access to food, RF only affected TRß1 mRNA expression and had no effect on the diurnal changes in TR1 and TR2. We conclude that liver TRß1 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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