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.
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.
Authors: Caterina Di Cosmo; Xiao-Hui Liao; Honggang Ye; Alfonso Massimiliano Ferrara; Roy E Weiss; Samuel Refetoff; Alexandra M Dumitrescu Journal: Endocrinology Date: 2013-09-12 Impact factor: 4.736
Authors: D Gallo; E Piantanida; G Veronesi; A Lai; L Sassi; V Lombardi; E Masiello; P Premoli; E Bianconi; C Cusini; S Rosetti; M L Tanda; A Toniolo; M Ferrario; L Bartalena Journal: J Endocrinol Invest Date: 2017-04-22 Impact factor: 4.256
Authors: W Edward Visser; Sigrid M A Swagemakers; Zeliha Ozgur; Rachel Schot; Frans W Verheijen; Wilfred F J van Ijcken; Peter J van der Spek; Theo J Visser Journal: Hum Mol Genet Date: 2010-08-12 Impact factor: 6.150
Authors: Hongyan Dong; Martin Paquette; Andrew Williams; R Thomas Zoeller; Mike Wade; Carole Yauk Journal: PLoS One Date: 2010-08-13 Impact factor: 3.240
Authors: Joao P Werneck-de-Castro; Tatiana L Fonseca; Daniele L Ignacio; Gustavo W Fernandes; Cristina M Andrade-Feraud; Lattoya J Lartey; Marcelo B Ribeiro; Miriam O Ribeiro; Balazs Gereben; Antonio C Bianco Journal: Endocrinology Date: 2015-07-27 Impact factor: 4.736