Thyroid hormone increases mRNA and protein expression of Na+-K+-ATPase alpha2 and beta1 subunits in human skeletal muscles.
BACKGROUND
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 alpha- and beta-subunits of the Na+-K+-ATPase.


METHODS
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 alpha2, but not alpha1 or alpha3, subunit was increased approximately 3-fold in pretreatment (2.98 +/- 0.52 vs. 0.95 +/- 0.40, P < 0.01), whereas that of beta1, not beta2 or beta3, 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 alpha2 and beta1 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 alpha2 and beta1, but not alpha1 or beta2, 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 alpha2 and beta1 subunits play the important role in this regulation.
Phakdeekitcharoen
Bunyong
B
Division of Nephrology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. RABPD@mucc.mahidol.ac.th
Phudhichareonrat
Suchart
S
Pookarnjanamorakot
Chathchai
C
Kijkunasathian
Chusak
C
Tubtong
Nattha
N
Kittikanokrat
Wassana
W
Radinahamed
Piyanuch
P
D000251:Adenosine Triphosphatases / Q000032:analysis / Q000235:genetics*; D000328:Adult; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000201:enzymology; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D018482:Muscle, Skeletal / Q000201:enzymology*; D021122:Protein Subunits; D012333:RNA, Messenger / Q000032:analysis*; D013963:Thyroid Hormones / Q000502:physiology*
D008565:Membrane Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; D013963:Thyroid Hormones; D000251:Adenosine Triphosphatases; C035123:magnesium sodium ATPase