TYPE-2 IODOTHYRONINE DEIODINASE IS HIGHLY EXPRESSED IN HUMAN THYROID

Type 2 iodothyronine deiodinase (D2) is a recently cloned selenodeiodi nase thought to provide intracellular 3,5,3' triiodothyronine (T3) to a restricted group of tissues, We report here the presence of D2 mRNA in human thyroid at levels 50-150-fold higher than in placenta, Surpri singly, while type 1 deiodinase (D1) is known to be present in human t hyroid, D2 has not been evaluated previously. D2 mRNA was especially h igh in thyroids from Graves' patients and in follicular adenomas, Stim ulated thyroids had higher D2 to D1 mRNA ratios than normal or multino dular glands suggesting differential regulation of D1 and D2 expressio n, Microsomes from normal, Graves', and TSH-stimulated thyroids contai ned low K-m D2 activity resistant to propylthiouracil (1 mM) or to ina ctivation by N-bromoacetyl T3, agents which block or inactivate D1, At 2 nM thyroxine (T4), 100 times the physiological-free T4 levels, 60-8 0% of T4 to T3 conversion in stimulated, but only 27% of that in norma l thyroids, is catalyzed by D2, We conclude that intrathyroidal T4 to T3 conversion by D2 may contribute significantly to the relative incre ase in thyroidal T3 production in patients with Graves' disease, toxic adenomas, and, perhaps, iodine deficiency.