In order to examine the question of whether thyroxine-binding globulin (TBG) influences significantly the peripheral metabolism of 3,3′,5-triiodo-L-thyronine (T3) in vivo, paired studies of the effects of a large intravenous load of L-thyroxine (T4) on the kinetics of 131I-labeled T3 metabolism were carried out in five normal subjects. After the T4 load, both the early distributive loss of labeled T3 from serum and the volume of T3 distribution, observed after distribution equilibrium had been attained, were greatly increased. These alterations were consistent with those to be expected from displacement of T3 from its extracellular binding sites. After the T4 load, however, the fractional rate of T3 turnover was decreased. This finding is ascribed either to competition between T3 and T4 for common intracellular pathways of degradation or excretion or to displacement of T3 from sites of more rapid to sites of less rapid metabolism. These effects of alterations in the binding activity of TBG on the peripheral metabolism of T3, together with those previously reported by others, are consistent with the interpretation that T3 is significantly bound by TBG in vivo. However, it is suggested that the effects of alterations in the T3-TBG binding interaction on the metabolism of T3 are obscured by alterations in the extracellular-cellular partitioning of T4 that would result from concurrent alterations in T4-binding by TBG.
Kenneth A. Woeber, Exequiel Hecker, Sidney H. Ingbar
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