The hypothesis that thyroid calorigenesis is mediated by stimulation of active Na(+) transport was tested by measuring the Q(o2) of liver slices and skeletal muscle (diaphragm) from thyroxine- and triiodothyronine-injected thyroidectomized and normal rats in media fortified with ouabain (10(-3) M) and/or free of Na(+) or K(+). In both tissues, more than 90% of the increase in Q(o2) produced by injections of thyroid hormone in euthyroid rats was derived from increased energy utilization by the Na(+) pump. In triiodothyronine-treated thyroidectomized rats, activation of Na(+) transport accounted for 90% or more of the increment in Q(o2) in liver and 40% or more of the increment in diaphragm. Intracellular Na(+), K(+), and Cl(-) concentrations were measured in euthyroid and hyperthyroid liver and diaphragm. The transmembrane Na(+) and K(+) concentration differences were significantly increased in both tissues by the administration of triiodothyronine. These results indicate that thyroid hormone activates Na(+) extrusion and K(+) accumulation either by increasing the local concentration of ATP or by direct stimulation of the Na(+) pump.
