CLONING OF THE MAMMALIAN TYPE-II IODOTHYRONINE DEIODINASE - A SELENOPROTEIN DIFFERENTIALLY EXPRESSED AND REGULATED IN HUMAN AND RAT-BRAIN AND OTHER TISSUES

The deiodination of thyroid hormones in extrathyroidal tissues plays a n important role in modulating thyroid hormone action. The type II dei odinase (DII) converts thyroxine to the active hormone 3,5,3'-triiodot hyronine, and in the rat is expressed in the brain, pituitary gland, a nd brown adipose tissue (BAT). Complementary DNAs (cDNAs) for the type s I and III deiodinases (DI and DIII, respectively) have been isolated and shown to code for selenoproteins. However, information concerning the structure of the mammalian DII remains limited, and the pattern o f its expression in human tissues is undefined. we report herein the i dentification and characterization of rat and human DII cDNAs. Both co de for selenoproteins and exhibit limited regions of homology with the DI and DIII. In the rat pituitary and BAT, DII mRNA levels are altere d more than 10-fold by changes in the thyroid hormone status of the an imal. Northern analysis of RNA derived from human tissues reveals expr ession of DII transcripts in heart, skeletal muscle, placenta, fetal b rain, and several regions of the adult brain. These studies demonstrat e that: (a) the rat and human DII are selenoproteins, (b) DII expressi on in the rat is regulated, at least in part, at the pretranslational level in some tissues, and (c) DII is likely to be of considerable phy siologic importance in throid hormone economy in the human fetus and a dult.