THYROID-HORMONE SPECIFICALLY REGULATES SKELETAL-MUSCLE NA-K+-ATPASE ALPHA-2-ISOFORMS AND BETA-2-ISOFORMS()

The purpose of this study was to determine the pattern of thyroid horm one (triiodothyronine, T3) regulation of the Na+-K+-adenosinetriphosph atase (Na+-K+-ATPase) alpha- and beta-subunit expression in skeletal m uscle, which expresses alpha1-, alpha2-, beta1-, and beta2-subunits, a nd compare it with that seen in kidney, which expresses only alpha1 an d beta1. Three steady states were studied: hypothyroid, euthyroid, and hyperthyroid (hypothyroids injected daily with 1 mug T3/g body wt for 2-16 days). Protein and mRNA abundance, determined by Western and Nor thern analysis, were normalized to a constant amount of homogenate pro tein and total RNA, respectively. In skeletal muscle, there was no cha nge in alpha1- or beta1-mRNA or protein levels in the transition from hypothyroid to hyperthyroid. However, alpha2 was highly regulated; mRN A reached a new steady-state level of fivefold over hypothyroid by 8 d ays of T3 treatment and protein abundance increased threefold. In addi tion, beta2-mRNA and protein were detected in skeletal muscle and were also highly regulated by T3; beta2-mRNA increased nearly fourfold ove r hypothyroid level, and beta2-protein abundance increased over twofol d. In kidney in the transition from hypothyroid to hyperthyroid, there were coordinate 1.6-fold increases in both alpha1- and beta1-mRNA abu ndance that predicted the observed changes in alpha1- and beta1-protei n levels and Na+-K+-ATPase activity. In conclusion, 1) alpha2 and beta 2 are highly regulated by T3 in skeletal muscle and the euthyroid leve ls of expression are dependent on the hormone, suggesting that the T3- responsive enzyme in rat skeletal muscle is an alpha2beta2-heterodimer , and 2) the effect of T3 on the expression of alpha1 and beta1 are ti ssue specific.