IDENTIFICATION OF A 57-KILODALTON SELENOPROTEIN IN HUMAN THYROCYTES AS THIOREDOXIN REDUCTASE AND EVIDENCE THAT ITS EXPRESSION IS REGULATED THROUGH THE CALCIUM-PHOSPHOINOSITOL SIGNALING PATHWAY

Human thyrocytes incubated with the phorbol ester, phorbol 12-myristat e 13-acetate (PMA; 10(-5)-10(-8) mol/L) and the calcium ionophore A231 87 (10(-5)-10(-8) mol/L) showed a marked increase in the expression of a 57-kDa selenoprotein identified as thioredoxin reductase (TR). Afte r the addition of A23187 with PMA, a significant induction in TR expre ssion 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 ha d no effect on TR expression, nor did these agents influence the induc tion of TR brought about by the addition of A23187 and PMA. These data show that the calcium-phosphoinositol second messenger cascade that c ontrols hydrogen peroxide generation in the human thyrocyte is also an important stimulator of TR expression. The role of TR in the thyrocyt e is unclear, but the selenoenzyme has a high capacity to detoxify com pounds, such as hydrogen peroxide and lipid hydroperoxides, that are p roduced in high concentration during thyroid hormone synthesis.