Patterns of liver gene expression governed by TRbeta.
Patterns of liver gene expression governed by TRbeta.
复制标题
DOI：
10.1210/mend.16.6.0846
复制
发表时间：
2002-06
影响因子：
--
通讯作者：
A. Flores-Morales;H. Gullberg;L. Fernández;N. Ståhlberg;N. Lee;B. Vennström;G. Norstedt
中科院分区：
文献类型：
--
作者：
A. Flores-Morales;H. Gullberg;L. Fernández;N. Ståhlberg;N. Lee;B. Vennström;G. Norstedt
肝脏中的多种代谢过程受甲状腺激素 (T3) 的调节。正常和 TRbeta 缺陷小鼠品系的肝脏基因表达谱应该可以对 T3 的快速和持续效应进行分类，并鉴定依赖于 TRbeta 的靶基因。使用 cDNA 微阵列分析了甲状腺功能减退和甲状腺功能亢进野生型以及 TRbeta 缺陷小鼠肝脏中约 4000 个基因的即时和长期 T3 调节。人们发现T3可以调节200多个基因，其中有100多个以前没有被描述过。所有这些基因中 60% 的 T3 调节依赖于 TRbeta 基因，表明 TRalpha1 可能在肝脏中具有以前未知的功能。基因表达模式分析显示，T3 的快速（2 小时）作用和持续 T3 治疗 5 天后观察到的晚期效应之间存在明显的功能区别。许多代谢活动被迅速执行，而对线粒体功能的影响，例如，在持续的 T3 治疗后可见。与野生型对照相比，TRbeta-/-小鼠表现出一些靶基因的表达升高，而其他靶基因的水平降低，表明肝脏中TR的直接和间接基因调节是复杂的，并且涉及主要TR亚型的配体依赖性和非配体依赖性作用。
Several metabolic processes in the liver are regulated by thyroid hormone (T3). Gene expression profiles of livers from normal and TRbeta-deficient mouse strains should allow the classification of rapid and sustained effects of T3, as well as identification of target genes that are dependent on TRbeta. The immediate and long-term T3 regulation of about 4000 genes in livers from hypo- and hyperthyroid wild-type and TRbeta-deficient mice was analyzed using cDNA microarrays. T3 was found to regulate more than 200 genes, and among these, more than 100 were previously not described. Sixty percent of all these genes show dependence on the TRbeta gene for T3 regulation, indicating that TRalpha1 may have previously unknown functions in the liver. Analysis of the gene expression patterns showed a clear functional distinction between rapid (2 h) actions of T3 and late effects, seen after 5 d of sustained T3 treatment. Many metabolic actions were rapidly executed, whereas effects on mitochondrial function, for example, were seen after the sustained T3 treatment. As compared with wild-type controls, TRbeta-/-mice exhibited elevated expression of some target genes and reduced levels of others, indicating that both direct and indirect gene regulation by TRs in liver is complex and involves both ligand-dependent and -independent actions by the major TR isoforms.