NUTRITIONAL AND HORMONAL-REGULATION OF THYROID-HORMONE DEIODINASES

Selenocysteine has been identified in the active center of types 1 and 3 iodothyronine deiodinases, two important enzymes regulating the for mation and degradation of the active thyroid hormone, 3,5,3'-triiodoth yronine (T3). Selenium is thus required for such complex processes as normal growth, brain development, and metamorphosis, all of which are thyroid hormone dependent. Structural and functional analyses of the t ype 1 deiodinase mRNA allowed identification of the selenocysteine ins ertion sequence (SECIS) element, a stem-loop structure in the 3' untra nslated region of the mRNA. SECIS elements with conserved sequence and structural features are also present in the 3' untranslated regions o f the mRNAs encoding selenoprotein P and the glutathione peroxidase fa mily of selenoproteins. These elements are necessary and sufficient fo r directing selenocysteine incorporation into the deiodinases and the other mammalian selenoproteins.