Effects of ligand and thyroid hormone receptor isoforms on hepatic gene expression profiles of thyroid hormone receptor knockout mice.

Paul M Yen, Xu Feng, Frederic Flamant, Yidong Chen, Robert L Walker, Roy E Weiss, Olivier Chassande, Jacques Samarut, Samuel Refetoff, Paul S Meltzer

Molecular Regulation and Neuroendocrinology Section, Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases/NIH, Room 8D12, Building 10, Bethesda, MD 20892, USA. pauly@intra.niddk.nih.gov

EMBO reports 2003 Jun

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Little is known about the overall patterns of thyroid hormone (Th)-mediated gene regulation by the main Th receptor (Tr) isoforms, Tr-alpha and Tr-beta, in vivo. We used 48 complementary DNA microarrays to examine hepatic gene expression profiles of wild-type and Thra and Thrb knockout mice under different Th conditions: no treatment, treatment with 3,3',5-triiodothyronine (T(3)), Th-deprivation using propylthiouracil (PTU), and treatment with a combination of PTU and T(3). Hierarchical clustering analyses showed that positively regulated genes fit into three main expression patterns. In addition, only a subpopulation of target genes repressed basal transcription in the absence of ligand. Interestingly, Thra and Thrb knockout mice showed similar gene expression patterns to wild-type mice, suggesting that these isoforms co-regulate most hepatic target genes. Differences in the gene expression patterns of Thra/Thrb double-knockout mice and Th-deprived wild-type mice show that absence of receptor and of hormone can have different effects. This large-scale study of hormonal regulation reveals the functions of Th and of Tr isoforms in the regulation of gene expression patterns.

Citation

Paul M Yen, Xu Feng, Frederic Flamant, Yidong Chen, Robert L Walker, Roy E Weiss, Olivier Chassande, Jacques Samarut, Samuel Refetoff, Paul S Meltzer. Effects of ligand and thyroid hormone receptor isoforms on hepatic gene expression profiles of thyroid hormone receptor knockout mice. EMBO reports. 2003 Jun;4(6):581-7