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WILLIAM T. CEFALU, WILLIAM M. PARDRIDGE, BHARTUR N. PREMACHANDRA, Hepatic Bioavailability of Thyroxine and Testosterone in Familial Dysalbuminemic Hyperthyroxinemia, The Journal of Clinical Endocrinology & Metabolism, Volume 61, Issue 4, 1 October 1985, Pages 783–786, https://doi.org/10.1210/jcem-61-4-783
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Abstract
The bioavailability of [125I]T4 or [3H]testosterone in serum obtained from normal subjects and from subjects with familial dysalbuminemic hyperthyroxinemia (FDH) was studied with a portal vein injection technique in ketamineanesthetized rats. In the present studies this technique was modified by performing uptake measurements in the presence of serum loaded with either 25 μM T4 or 1 μM testosterdrte. Loading of serum with these high concentrations displaced the labeled hormone from the lower capacity globulin or prealbuminbinding sites to the high capacity albumin or dysalbumin-binding sites, and allowed for the analysis of hormone availability in liver when the labeled hormone was delivered to the tissue bound either to albumin or to dysalbumin binding sites. In the presence of normal serum, 33 ± 3% (SE) of T4 was available to rat liver, as opposed to 20 ± 2% for FDH serum. When normal serum was loaded with 25 fiM T4, the bioavailable T4 increased to 97 ± 2%, consistent with the availability of T4 bound to albumin. However, the hepatic bioavailability of T4 in the presence of 25 μM T4 in FDH serum was only 33 ± 4%. Testosterone bioavailability was similar in normal and in FDH sera, and was 49 ± 7% in the absence and 99 ± 4% in the presence of 1 fiM testosterone.
These studies suggest that T4 bound to the FDH albumin binding site is not readily available for entry into liver, whereas T4 bound to the normal albumin binding site is freely available for uptake in vivo. The differential bioavailability of T4 is compatible with the model that the normal and FDH binding sites are situated on different parts of the albumin molecule, and that only T4 bound to the normal binding site is freely available for delivery to the liver.
