Thyroid hormone coordinately regulates Na+-K+-ATPase alpha- and beta-subunit mRNA levels in kidney

Synthesis of the sodium pump, Na+-K+-ATPase, is regulated by thyroid hormone in responsive tissues. The purpose of this study was to determine if triiodothyronine (T3) regulates the concentration of the mRNAs coding for the two enzyme subunits, alpha and beta, and the time course of the response. A single dose of T3 (250 micrograms/100 g body wt) was administered to hypothyroid rats that were killed at various times after injection. In the kidney cortexes of the T3-injected animals, as well as hypothyroid and euthyroid rats, alpha- and beta-mRNA concentrations were measured by dot blot using cDNAs corresponding to the two mRNAs; alpha-subunit abundance was measured by Western blot using antibodies to the enzyme, and Na+-K+-ATPase activity was measured enzymatically. alpha- and beta-mRNAs increased coordinately, after a 6-h time lag to 1.6-fold over hypothyroid levels by 12 h after T3. alpha-Subunit abundance increased significantly by 48 h and to 1.4-fold over hypothyroid by 72 h after T3. Na+-K+-ATPase activity increased with the same time course as the increase in alpha-subunit abundance to 1.3-fold over hypothyroid by 72 h after T3. We conclude that T3 regulates Na+-K+-ATPase synthesis and activity by coordinately increasing the mRNAs of both the alpha- and beta-subunits of the enzyme.