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Thyroid Hormone Increases mRNA and Protein Expression of Na⁺-K⁺-ATPase ₂ and ß₁ Subunits in Human Skeletal Muscles

Division of Nephrology, Department of Medicine (B.P., P.R.), and Departments of Orthopedics (C.P., C.K.) and Pathology (N.T.), Research Center (W.K.), Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand; and Department of Pathology (S.P.), Prasat Neurological Institute, Bangkok 10400, Thailand

Address all correspondence and requests for reprints to: Bunyong Phakdeekitcharoen, Division of Nephrology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. E-mail: RABPD{at}mucc.mahidol.ac.th.

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 - and ß-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 ₂, but not ₁ or ₃, subunit was increased approximately 3-fold in pretreatment (2.98 ± 0.52 vs. 0.95 ± 0.40, P < 0.01), whereas that of ß₁, not ß₂ or ß₃, 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 ₂ and ß₁ 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 ₂ and ß₁, but not ₁ or ß₂, 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 ₂ and ß₁ subunits play the important role in this regulation.