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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, METHODS, METHODS, METHODS, RESULTS. Meshes: Adult, Female, Gene Expression Regulation, Glucose Transporter Type 5, Hormone Replacement Therapy, Humans, Male, MicroRNAs, Middle Aged, Muscle, Skeletal, Oligonucleotide Array Sequence Analysis, Thyroxine.
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Do physiological thyroid hormone levels regulate numerous skeletal muscle transcripts? Context: Skeletal muscle is an important target tissue for thyroid hormone (TH). It is currently unknown which genes are regulated by physiological TH levels. We examined the effects of l-thyroxine on human skeletal muscle transcriptome. Microarray analysis of transcript levels was performed using skeletal muscle biopsies from patients under euthyroid and hypothyroid conditions. The study was conducted in a university hospital laboratory. We studied skeletal muscle obtained from 10 thyroidectomized patients with differentiated thyroid carcinoma on and after 4 wk off L-thyroxine replacement. Gene expression changes were measured using microarrays. Results were analyzed using dedicated statistical methods. 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.
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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. Final Decision: yes