Diurnal variation in rat liver thyroid hormone receptor (TR)-alpha messenger ribonucleic acid (mRNA) is dependent on the biological clock in the suprachiasmatic nucleus, whereas diurnal variation of TR beta 1 mRNA is modified by food intake.
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 alpha 1 and TR alpha 2 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 TR beta 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 (RF) schedule, with one meal every 4 h. When compared with rats with free access to food, RF only affected TR beta 1 mRNA expression and had no effect on the diurnal changes in TR alpha 1 and TR alpha 2. We conclude that liver TR beta 1 expression is most clearly affected by food intake. Diurnal changes in liver TR alpha 1 and TR alpha 2 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 T(3)-dependent gene expression, which is supported by a diurnal variation in the expression of the 5'-deiodinase gene.
Zandieh Doulabi
B
B
Department of Endocrinology and Metabolism, Academic Medical Centre, 1105 AZ Amsterdam, The Netherlands.
Platvoet-Ter Schiphorst
M
M
Kalsbeek
A
A
Fliers
E
E
Bakker
O
O
Wiersinga
W M
WM
D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D004435:Eating / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D007536:Isomerism; D008099:Liver / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D037021:Thyroid Hormone Receptors alpha / Q000737:chemistry / Q000235:genetics*; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*
D012333:RNA, Messenger; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta