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. 1980 Aug;66(2):367–374. 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 1,2, Lawrence J Mietus 1,2
PMCID: PMC371719  PMID: 6772672

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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