3,3',5'-Triiodothyronine inhibits ontogenetic development of iodothyronine-5'-deiodinase in the liver of the neonatal mouse.
To elucidate the effect of rT3 on iodothyronine-5'-deiodinating activity (I-5'-DA) in the liver of neonatal mice, rT3 was injected sc on the 5-8th day after birth and I-5'-DA in the liver was determined. A single injection of rT3 (0.01-1 microgram/g) inhibited the ontogenetically developing I-5'-DA in a dose- and time-dependent manner. The inhibitory effect was reversible and specific for I-5'-DA. Lineweaver-Burk analysis revealed that the time- and dose-dependent decrease in the enzyme activity was due to a decrease in Vmax with no alteration in Km values (5 x 10(-8) mol/l). The maximal inhibitory effect was observed at a dose of 1 microgram rT3/g, whereas the inhibitory effect was diminished at greater doses (4-10 micrograms/g), probably owing to a contamination with T4 of the rT3 preparation administered. Furthermore, consistent with our previous in vitro findings, rT3 inhibited the I-5'-DA induced by T3 in the liver of neonatal mice. These findings suggest that rT3 inhibited I-5'-DA in the liver of neonatal mice by decreasing the amount of enzyme available to the substrate and that rT3 also elicited an antagonistic effect against T3 in the induction of I-5'-DA in vivo.
Han
D C
DC
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical College, Japan.
Sato
K
K
Fujii
Y
Y
Ozawa
M
M
Imamura
H
H
Tsushima
T
T
Shizume
K
K
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007453:Iodide Peroxidase / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D051379:Mice; D008815:Mice, Inbred Strains; D014285:Triiodothyronine, Reverse / Q000008:administration & dosage*
D014285:Triiodothyronine, Reverse; D007453:Iodide Peroxidase