Modeling Circadian Rhythms of Glucocorticoid Receptor and Glutamine Synthetase Expression in Rat Skeletal Muscle
Modeling Circadian Rhythms of Glucocorticoid Receptor and Glutamine Synthetase Expression in Rat Skeletal Muscle
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DOI：
10.1007/s11095-005-9608-3
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发表时间：
2006-02
影响因子：
3.7
通讯作者：
Zhenling Yao;D. DuBois;R. Almon;W. Jusko
中科院分区：
文献类型：
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作者：
Zhenling Yao;D. DuBois;R. Almon;W. Jusko
目的内源性皮质酮(CS)的昼夜节律可能引起正常大鼠下游基因表达的波动。方法健康雄性Wistar大鼠54只，在24 h内18个时间点(n=3)处死大鼠，测定血浆CS浓度、腓肠肌GR和GS基因表达及GS活性。正常大鼠骨骼肌GR、GS基因表达和GS活性呈昼夜节律变化。GR m RNA在血浆CS峰值后4h达低谷，组织−1在0.5 5~0.9g m ol之间波动，GS m RNA和活性在内源性CS峰值后6和12 h达到峰值。GSm RNA在3~6fmolg组织−1之间波动，而GS活性在17~23fmolminμ−1g蛋白−1之间波动。机制受体/基因介导的药效学模型用于描述GR m RNA、GS m RNA和GS活性在昼夜周期内的时间模式。结论所建立的模型能够反映正常大鼠骨骼肌组织中CS、GR和GS的昼夜表达模式，并显示组织基因表达对血浆CS的依赖关系。
PurposeThe circadian rhythm of endogenous corticosterone (CS) may produce fluctuations of downstream gene expression in normal rats. This study examined changes in glucocorticoid receptor (GR) and glutamine synthetase (GS) expression in rat skeletal muscle in relation to plasma CS over a 24-h period.MethodsFifty-four normal male Wistar rats were sacrificed at 18 time points (n= 3) over 24 h. Plasma CS concentrations and gastrocnemius muscle GR and GS mRNA and GS activity were measured.ResultsThe circadian rhythm of plasma CS was captured by a two-harmonic function. The expression of GR and GS mRNA and GS activity follow a circadian rhythm in normal rat skeletal muscle. GR mRNA reaches a trough at 4 h after the peak of plasma CS and it fluctuates between 0.55 and 0.9 fmol g tissue−1. GS mRNA and activity reach peaks at 6 and 12 h after the endogenous CS peak. GS mRNA oscillates between 3 and 6 fmol g tissue−1, whereas GS activity fluctuates between 17 and 23 μmol min−1g protein−1. Mechanistic receptor/gene-mediated pharmacodynamic models were applied to describe the temporal patterns of GR mRNA, GS mRNA, and GS activity within the circadian cycle.ConclusionsThe integrated models were able to capture the circadian expression patterns of plasma CS, and GR and GS in normal rat skeletal muscle showing a dependence of tissue gene expression on plasma CS.