Deconjugation of Thyroxine Glucuronide by the Rat Kidney

Background: Rapid deconjugation of administered thyroxine glucuronide (T4G) to thyroxine (T4) has been observed in human subjects. The goal of this study was to characterize, in the rat, the location and kinetics of this deconjugation process and to identify whether early conjugation of T4 to T4G occurs in the liver. Methods: Normal male rats received intraportal radiolabeled T4 and T4G. Tissues were assayed 1 to 15 minutes after the injection. Results: After T4G injection, assay of the kidneys, and to a lesser extent assay of the liver and plasma, showed presence of considerable T4, the result of deconjugation. In the kidneys, 79 +/- 12% (mean +/- SD%) of total (T4 + T4G) was in T4 form. In the liver and plasma, T4 was 10 +/- 9% and 6 +/- 5%, respectively, of the total (T4 + T4G). No significant conjugation of T4 occurred in any of the tissues assayed during this short time period. Secretion in the bile of administered T4G as T4G increased with time. Conclusions: These data, together with the previous observations in human subjects, suggest that T4G, with its greater tissue distribution, may serve as a medium for transfer of T4 into tissues not subject to direct transfer of T4 from the circulation. Hence, the true volume of distribution of T4 is postulated to be greater than that measured by tracer studies of T4 distribution.