Influx of Thyroid Hormones into Rat Liver In Vivo: <i>DIFFERENTIAL AVAILABILITY OF THYROXINE AND TRIIODOTHYRONINE BOUND BY PLASMA PROTEINS</i>

William M. Pardridge; Lawrence J. Mietus

doi:10.1172/JCI109865

Influx of Thyroid Hormones into Rat Liver In Vivo: DIFFERENTIAL AVAILABILITY OF THYROXINE AND TRIIODOTHYRONINE BOUND BY PLASMA PROTEINS

William M. Pardridge and Lawrence J. Mietus

Published August 1, 1980 - More info

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Abstract

The transport of [¹²⁵I]thyroxine (T₄) and [¹²⁵I]triiodothyronine (T₃) into liver was investigated with a tissue sampling-portal vein injection technique in the anesthetized rat. The method allows the investigation of the effects of plasma proteins in human serum on the unidirectional influx of T₄ or T₃ into liver cells. The percent extraction of unidirectional clearance of T₃ and T₄ was 77±2% and 43±2%, respectively, after portal injection of a bolus of Ringer's solution. Cell membrane transport of T₄ or T₃ was nonsaturable because 50-μM concentrations of unlabeled hormone had no effect on transport. The addition of bovine albumin in concentrations of 1, 5, or 10 g/100 ml bound >98% of T₄ or T₃ in vitro, but had no significant effect on T₃ or T₄ transport in vivo. Conversely, 10% rabbit antisera specific for T₃ or T₄, completely abolished the intracellular distribution of thyroid hormone into liver. In the presence of rat serum, which contains albumin and thyroid hormone binding pre-albumin (TBPA), 18 and 81% of total plasma T₄ and T₃, respectively, were available for transport in vivo. The fraction of hormone available for transport in the presence of normal human serum, which contains albumin, TBPA, and thyroid hormone binding globulin (TBG) was 11% for T₄ and 72% for T₃. The fraction of hormone transported into liver after injection of serum obtained from pregnant or birth control pilltreated volunteers was 4% for T₄ (but this was not significantly different from zero) and 54% for T₃.

These data suggest: (a) The mechanism by which T₄ and T₃ traverse the liver cell membrane is probably free diffusion. (b) Albumin-bound T₄ or T₃ is freely cleared by liver, ∼50% of TBG-bound T₃ is transported, but little, if any, of TBPA-bound T₄ or TBG-bound T₄ is cleared by liver cells. (c) Although the albumin-bound fraction of T₄ greatly exceeds the free (dialyzable) moiety, the two fractions are both inversely related to the existing TBA or TBG level; therefore, in vitro measurements of free T₄ would be expected to accurately reflect what is available for transport in vivo. Conversely, TBG-bound T₃ is readily transported in vivo; therefore, it is proposed that in vitro measurements of free T₃ do not reliably predict the fraction of T₃ available for transport into liver in vivo.