Physiological thyroid hormone levels regulate numerous skeletal muscle transcripts.
BACKGROUND
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.


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


METHODS
The study was conducted in a university hospital laboratory.


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


METHODS
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.


CONCLUSIONS
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.
Visser
W Edward
WE
Erasmus University Medical Center, Department of Internal Medicine, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. t.j.visser@erasmusmc.nl
Heemstra
Karen A
KA
Swagemakers
Sigrid M A
SM
Ozgür
Zeliha
Z
Corssmit
Eleonora P
EP
Burggraaf
Jacobus
J
van Ijcken
Wilfred F J
WF
van der Spek
Peter J
PJ
Smit
Johannes W A
JW
Visser
Theo J
TJ
D000328:Adult; D005260:Female; D005786:Gene Expression Regulation; D051296:Glucose Transporter Type 5 / Q000032:analysis; D020249:Hormone Replacement Therapy; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D013974:Thyroxine / Q000627:therapeutic use*
D051296:Glucose Transporter Type 5; D035683:MicroRNAs; C495726:SLC2A5 protein, human; D013974:Thyroxine