Human thyrocytes incubated with the phorbol ester, phorbol 12-myristate 13-acetate (PMA; 10(-5)-10(-8) mol/L) and the calcium ionophore A23187 (10(-5)-10(-8) mol/L) showed a marked increase in the expression of a 57-kDa selenoprotein identified as thioredoxin reductase (TR). After the addition of A23187 with PMA, a significant induction in TR expression was observed after 6 h, with maximal induction occurring by 24 h. The addition of 8-bromo-cAMP (10(-4) mol/L) or TSH (10 U/L) alone had no effect on TR expression, nor did these agents influence the induction of TR brought about by the addition of A23187 and PMA. These data show that the calcium-phosphoinositol second messenger cascade that controls hydrogen peroxide generation in the human thyrocyte is also an important stimulator of TR expression. The role of TR in the thyrocyte is unclear, but the selenoenzyme has a high capacity to detoxify compounds, such as hydrogen peroxide and lipid hydroperoxides, that are produced in high concentration during thyroid hormone synthesis.