Activation and inactivation of thyroid hormone by type I iodothyronine deiodinase.
The prohormone thyroxine (T4) is activated by outer ring deiodination (ORD) to 3,3',5-triiodothyronine (T3) and both hormones are degraded by inner ring deiodination (IRD) to 3,3',5'-triiodothyronine (rT3) and 3,3'-diiodothyronine, respectively. Indirect evidence suggests that the type I iodothyronine deiodinase (ID-I) in liver has both ORD and IRD activities, with preference for rT3 and sulfated iodothyronines as substrates. To establish this, we have compared the ORD of rT3 and IRD of T3 and T3 sulfate by homogenates of cells transfected with rat ID-I cDNA and by rat liver microsomes. In both preparations rT3 is the preferred substrate, while deiodination of T3 is markedly accelerated by its sulfation. Kinetic analysis provided similar Km and Vmax values in cell homogenates and liver microsomes. These data demonstrate unequivocally that ID-I is capable of both activating and inactivating thyroid hormone by ORD and IRD, respectively.
Moreno
M
M
Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands.
Berry
M J
MJ
Horst
C
C
Thoma
R
R
Goglia
F
F
Harney
J W
JW
Larsen
P R
PR
Visser
T J
TJ
D000818:Animals; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D004622:Embryo, Mammalian; D015870:Gene Expression; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism*; D007668:Kidney; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013431:Sulfates / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism*; D014162:Transfection; D014284:Triiodothyronine / Q000378:metabolism; D014285:Triiodothyronine, Reverse / Q000378:metabolism
D018076:DNA, Complementary; D013431:Sulfates; D014284:Triiodothyronine; D014285:Triiodothyronine, Reverse; D007453:Iodide Peroxidase; D013974:Thyroxine