This Article Full Text Full Text (PDF) Supplemental Data Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Google Scholar Articles by Visser, W. E. Articles by Visser, T. J. PubMed PubMed Citation Articles by Visser, W. E. Articles by Visser, T. J. Related Collections Thyroid Metabolism

Physiological Thyroid Hormone Levels Regulate Numerous Skeletal Muscle Transcripts

Departments of Internal Medicine (W.E.V., T.J.V.), Bioinformatics (S.M.A.S., P.J.v.d.S.), and Genetics (S.M.A.S.), Center for Biomics (Z.O., W.F.J.v.I.), Erasmus Medical Center, 3015 CE Rotterdam, The Netherlands; Department of Endocrinology and Metabolic Diseases (K.A.H., E.P.C., J.W.A.S.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; and Center for Human Drug Research (J.B.), 2333 CL Leiden, The Netherlands

Address all correspondence and requests for reprints to: Theo J. Visser, Ph.D., Erasmus University Medical Center, Department of Internal Medicine, Room Ee 502, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail: t.j.visser{at}erasmusmc.nl.

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.