title: In vivo regulation of human skeletal muscle gene expression by thyroid hormone.
abstract: Thyroid hormones are key regulators of metabolism that modulate transcription via nuclear receptors. Hyperthyroidism is associated with increased metabolic rate, protein breakdown, and weight loss. Although the molecular actions of thyroid hormones have been studied thoroughly, their pleiotropic effects are mediated by complex changes in expression of an unknown number of target genes. Here, we measured patterns of skeletal muscle gene expression in five healthy men treated for 14 days with 75 microg of triiodothyronine, using 24,000 cDNA element microarrays. To analyze the data, we used a new statistical method that identifies significant changes in expression and estimates the false discovery rate. The 381 up-regulated genes were involved in a wide range of cellular functions including transcriptional control, mRNA maturation, protein turnover, signal transduction, cellular trafficking, and energy metabolism. Only two genes were down-regulated. Most of the genes are novel targets of thyroid hormone. Cluster analysis of triiodothyronine-regulated gene expression among 19 different human tissues or cell lines revealed sets of coregulated genes that serve similar biologic functions. These results define molecular signatures that help to understand the physiology and pathophysiology of thyroid hormone action.
authors.affiliation: Department of Pediatrics and Genetics, Howard Hughes Medical Institute, Beckman Center, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.forename: Nathalie
authors.initials: N
authors.lastname: Viguerie
authors.forename: Maximilian
authors.initials: M
authors.lastname: Diehn
authors.forename: Ash
authors.initials: A
authors.lastname: Alizadeh
authors.forename: Pierre
authors.initials: P
authors.lastname: Barbe
authors.forename: Claire
authors.initials: C
authors.lastname: Thalamas
authors.forename: John D
authors.initials: JD
authors.lastname: Storey
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Brown
authors.forename: Greg S
authors.initials: GS
authors.lastname: Barsh
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
mesh_terms: D000284:Administration, Oral; D000328:Adult; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014284:Triiodothyronine / Q000008:administration & dosage* / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D014284:Triiodothyronine