These results clearly demonstrate that Se levels are regulated by TRα1: in euthyroid TRα1+m mice, the mutant TRα1 suppresses serum Se due to its potent aporeceptor activity (comparable to the situation found in hypothyroidism), whereas high levels of TH (either by oral T3 treatment or genetically by crossbreeding to hyperthyroid TRβ−/− mice) activate TRα1 and confer an increase in serum Se even in the absence of TRβ. The gene discussed is TH; the disease is hypothyroidism.