Effects of thyrotropin on sodium potassium-ATPase in rat thyroid

The glycoprotein hormone thyrotropin (TSH) is the major regulator of thyroid hormone (T4 and T3) biosynthesis. A critical step in thyroid hormone production is the accumulation of iodide against its concentration gradient. A specialized transporter (Na*, Lsymporter; NIS) in the basal membrane of thyroid follicular cells fecilitates the uptake of r into the cell coupled with Na*. The Na, K-ATPase (Na, K-piunp) maintains a low intracellular Na* concentration, thus provides the driving force necessary for Na*-coupled transport. The Na, K-ATPase is a membrane spanning enzyme complex that extrudes 3 Na* in exchange for 2 K* at the expense of ATP. This enzyme consists of a catalytic asubunit and a glycosylated p-subimit and functions in the basal membrane as an apheterodimer. I investigated the effects of thyrotropin on the abundance of the Na, KATPase and its activity. Serum TSH levels were lowered in rats with triiodothyronine, the negative feedback inhibitor of TSH synthesis and secretion (10|ig/g/day for one week). Propylthiouracil, a powerful inhibitor of thyroid hormone synthesis, was administered (0.1% in drinking water) to raise endogenous TSH. Na, K-ATPase abundance was evaluated by gel electrophoresis and immunoblotting techniques that utilized antibodies specific for both subunits. Hyperthyroid rats had a 75% reduction in a-subunit protein, but p-subunit abundance did not change. Futhermore, hypothyroid rats yielded 136% and 567% increases in a and p-subunit proteins, respectively. Na, K-ATPase enzyme activity was also studied. Lowering TSH did not significantly alter enzyme activity, but increasing TSH produced a dramatic four-fold increase in enzyme activity. These data suggest that thyrotropin regulates Na, K-ATPase abundance and enzyme activity in thyroid follicular cells.