Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans.
The relative roles of the types 1 and 2 iodothyronine deiodinases (D1 and D2) in extrathyroidal 3,5,3'-triiodothyronine (T3) production in humans are unknown. We calculated the rate of thyroxine (T4) to T3 conversion by intact cells transiently expressing D1 or D2 at low (2 pM), normal (20 pM), and high (200 pM) free T4 concentrations. Deiodinase activities were then assayed in cell sonicates. The ratio of T3 production in cell sonicates (catalytic efficiency) was multiplied by the tissue activities reported in human liver (D1) and skeletal muscle (D2). From these calculations, we predict that in euthyroid humans, D2-generated T3 is 29 nmol/d, while that of D1-generated T3 is 15 nmol/d, from these major deiodinase-expressing tissues. The total estimated extrathyroidal T3 production, 44 nmol/d, is in close agreement with the 40 nmol T3/d based on previous kinetic studies. D2-generated T3 production accounts for approximately 71% of the peripheral T3 production in hypothyroidism, but D1 for approximately 67% in thyrotoxic patients. We also show that the intracellular D2-generated T3 has a greater effect on T3-dependent gene transcription than that from D1, which indicates that generation of nuclear T3 is an intrinsic property of the D2 protein. We suggest that impairment of D2-generated T3 is the major cause of the reduced T3 production in the euthyroid sick syndrome.
Maia
Ana Luiza
AL
Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Kim
Brian W
BW
Huang
Stephen A
SA
Harney
John W
JW
Larsen
P Reed
PR
D002460:Cell Line; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D015394:Molecular Structure; D018482:Muscle, Skeletal / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism*; D013974:Thyroxine / Q000737:chemistry / Q000378:metabolism; D014284:Triiodothyronine / Q000097:blood* / Q000737:chemistry; D000097564:Iodothyronine Deiodinase Type II
D007453:Iodide Peroxidase; D007457:Iodine Radioisotopes; D013974:Thyroxine; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II; C109812:iodothyronine deiodinase type I