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J Clin Endocrinol Metab. 2009 Sep;94(9):3487-96. doi: 10.1210/jc.2009-0782. Epub 2009 Jun 30.

Physiological thyroid hormone levels regulate numerous skeletal muscle transcripts.

Author information

1
Erasmus University Medical Center, Department of Internal Medicine, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. t.j.visser@erasmusmc.nl

Abstract

CONTEXT:

Skeletal muscle is an important target tissue for thyroid hormone (TH). It is currently unknown which genes are regulated by physiological TH levels.

OBJECTIVE:

We examined the effects of l-thyroxine on human skeletal muscle transcriptome.

DESIGN:

Microarray analysis of transcript levels was performed using skeletal muscle biopsies from patients under euthyroid and hypothyroid conditions.

SETTING:

The study was conducted in a university hospital laboratory.

PATIENTS:

We studied skeletal muscle obtained from 10 thyroidectomized patients with differentiated thyroid carcinoma on and after 4 wk off L-thyroxine replacement.

MEAN OUTCOME MEASURES:

Gene expression changes were measured using microarrays. Results were analyzed using dedicated statistical methods.

RESULTS:

We detected 607 differentially expressed genes on L-thyroxine treatment, of which approximately 60% were positively and approximately 40% were negatively regulated. Representative genes were validated by quantitative PCR. Genes involved in energy and fuel metabolism were overrepresented among the up-regulated genes, of which a large number were newly associated with thyroid state. L-thyroxine therapy induced a large down-regulation of the primary transcripts of the noncoding microRNA pair miR-206/miR-133b.

CONCLUSION:

We demonstrated that physiological levels of TH regulate a myriad of genes in human skeletal muscle. The identification of novel putatively TH-responsive genes may provide the molecular basis of clinical effects in subjects with different TH status. The observation that TH regulates microRNAs reveals a new layer of complexity by which TH influences cellular processes.

PMID:
19567520
DOI:
10.1210/jc.2009-0782
[Indexed for MEDLINE]

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