AJP - Gastrointestinal and Liver Physiology, Vol 248, Issue 5 545-G550, Copyright © 1985 by American Physiological Society
Transport of thyroxine bound to human prealbumin into rat liver
W. M. Pardridge, B. N. Premachandra and G. Fierer
The transport into rat liver of thyroxine (T4) bound to human prealbumin
was studied with the use of sera obtained from patients with thyroid
hormone-binding globulin (TBG) deficiency and with purified human
prealbumin. The unidirectional extraction of 125I-T4 by liver was measured
after rapid injection of isotope mixed in human serum into the portal vein
of ketamine-anesthetized rats. The percentage of total serum T4 transported
into liver was 47.6 +/- 5.2% in subjects with TBG deficiency, and this
represented a 50% increase in hepatic T4 transport relative to control
human serum. Since T4 is bound to albumin and to prealbumin in complete TBG
deficiency, these results suggested that T4 bound to human prealbumin was
transported into rat liver. This was confirmed using portal vein injections
of human prealbumin at physiological concentrations (0.1-0.3 mg/ml). At
these concentrations, T4 bound to human prealbumin was readily transported
into liver. These studies suggest factors present in the liver
microcirculation inhibit the binding of T4 to human prealbumin such that T4
bound to human prealbumin is highly transportable in liver; conversely, T4
bound to rat prealbumin is not transportable in rat liver. The inability of
human prealbumin to sequester T4 in plasma may provide the basis for the
selective advantage in humans of TBG, which does sequester T4 in plasma.
