AJP - Endocrinology and Metabolism, Vol 257, Issue 5 E764-E771, Copyright © 1989 by American Physiological Society
Modeling thyroxine transport to liver: rejection of the "enhanced dissociation" hypothesis as applied to thyroxine
C. M. Mendel
Cardiovascular Research Institute, Liver Center, San Francisco, California 94143-0130.
Three models for the hepatic uptake of thyoxine (T4) from human plasma were
considered: 1) uptake occurs exclusively via the pool of free T4 after
spontaneous dissociation of T4-plasma-protein complexes, 2) uptake occurs
primarily via the pool of bound T4 by the interaction of one or more
binding proteins with the cell-surface membrane, and 3) uptake occurs
primarily by "enhanced dissociation" of T4 from one or more of its binding
proteins within the sinusoids. Each of these models was examined in
relation to well-accepted unidirectional uptake and steady-state kinetics
data that indicate that 1) between 4 and 24% of the T4 in normal human
serum is taken up unidirectionally by the liver in a single pass, and 2)
the in vivo disposal rate of T4 is unaffected by primary changes in the
plasma concentration of thyroid hormone-binding globulin. Both analytical
and numerical techniques were used. The first two models were found to be
compatible with both the steady-state kinetics data and the unidirectional
uptake data, given certain assumptions in each of the models. Although
theoretically distinguishable on the basis of unidirectional uptake data,
uncertainty over the true uptake (influx) rate constant for free T4
prevented resolution between these two models. In contrast, the third
model, that of enhanced dissociation [W. M. Pardridge, Am. J. Physiol. 252
(Endocrinol. Metab. 15): E157-E164, 1987], was found, as currently
formulated with respect to T4, to be incompatible with both the
steady-state kinetics data and the unidirectional uptake data.(ABSTRACT
TRUNCATED AT 250 WORDS)
