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

EMBO Rep. 2003 Jun;4(6):581-7. doi: 10.1038/sj.embor.embor862.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cluster Analysis
  • DNA, Complementary / metabolism
  • Down-Regulation
  • Gene Expression Regulation*
  • Genotype
  • Ligands
  • Liver / metabolism*
  • Mice
  • Mice, Knockout
  • Nucleic Acid Hybridization
  • Oligonucleotide Array Sequence Analysis
  • Propylthiouracil / pharmacology
  • Protein Isoforms
  • Thyroid Hormone Receptors alpha / chemistry
  • Thyroid Hormone Receptors alpha / genetics*
  • Thyroid Hormone Receptors beta / chemistry
  • Thyroid Hormone Receptors beta / genetics*
  • Triiodothyronine, Reverse / pharmacology
  • Up-Regulation


  • DNA, Complementary
  • Ligands
  • Protein Isoforms
  • Thyroid Hormone Receptors alpha
  • Thyroid Hormone Receptors beta
  • Triiodothyronine, Reverse
  • Propylthiouracil