In Vivo Regulation of Human Skeletal Muscle Gene Expression by Thyroid Hormone
Open accessAbstract
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 μg 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. [The list of transcripts corresponding to up-regulated and down-regulated genes is available as a web supplement at http://www.genome.org.]
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The gene expression changes were validated by reverse transcription and RTqPCR.
“We validated the gene expression changes by reverse transcription and RTqPCR, performed as described in [63].”
From Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity (2008) · cites this paper as [63]
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References 51 · Cited by 169
- Authors
- Clément, K., Viguerie, N., Diehn, M., Alizadeh, A., Barbe, P., Thalamas, C., Storey, J. D., Brown, P. O., Barsh, G. S., & Langin, D.
- Affiliations
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2002-02-01
- Volume
- 12
- Issue
- 2
- Pages
- 281-291
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- PMC
- PMC155277
- OpenAlex
- W2111766088
- Cited by
- 169
- References
- 51
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 6 · 2020: 8 · 2019: 2 · 2018: 5 · 2017: 11 · 2016: 5 · 2015: 9 · 2014: 6 · 2013: 8 · 2012: 7
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Eli Lilly and Company
- Institut National de la Santé et de la Recherche Médicale (4P007E)
- Centre National de la Recherche Scientifique
- Servier
- Institut de Recherches Servier
- National Institute of General Medical Sciences (5T32 GM-07365, T32GM007365, GM 07365)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- thyroid hormones, triiodothyronine, skeletal muscle, gene expression regulation, hyperthyroidism, nuclear receptors, transcriptional regulation, mRNA maturation, protein turnover, energy metabolism, signal transduction, co-regulated genes, false discovery rate estimation
- MeSH terms
- Administration, Oral, Adult, Cytoskeletal Proteins, Gene Expression Regulation, Humans, Male, RNA, Messenger, Transcription Factors, Triiodothyronine, Down-Regulation, Up-Regulation, Muscle, Skeletal, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling
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