Thyroid Hormone Increases mRNA and Protein Expression of Na+-K+-ATPase α2 and β1 Subunits in Human Skeletal Muscles

Context: Thyroid hormone regulates specific Na+-K+-ATPase isoforms in rodent skeletal muscles. No study has examined this relationship in human tissues. Objective: This study investigated the effect of hyperthyroid status on the expression of the α- and β-subunits of the Na+-K+-ATPase. Design: The vastus lateralis muscles from eight hyperthyroid patients were biopsied before and after treatment. Ten age-matched euthyroid subjects served as controls. Results: In hyperthyroid patients, the average T3 level was three times higher in pretreatment compared with posttreatment (262 ± 75 vs. 86 ± 21 ng/dl, P = 0.001). The relative mRNA expression of the α2, but not α1 or α3, subunit was increased approximately 3-fold in pretreatment (2.98 ± 0.52 vs. 0.95 ± 0.40, P < 0.01), whereas that of β1, not β2 or β3, subunit was increased approximately 2.8-fold in pretreatment (2.83 ± 0.38 vs. 1.10 ± 0.27, P < 0.01). The relative mRNA expression of the α2 and β1 subunits was positively correlated with the serum T3 (r = 0.75, P = 0.001 and r = 0.66, P = 0.003, respectively). Immunohistochemistry studies revealed an increase in protein abundance of the α2 and β1, but not α1 or β2, subunits in the plasma membrane of muscle fibers of hyperthyroid patients, which decreased after treatment. Conclusions: This provides the first evidence that, in human skeletal muscles, thyroid hormone up-regulates the Na+-K+-ATPase protein expression at least, in part, at mRNA level, and the α2 and β1 subunits play the important role in this regulation.