PCBs are nearly ubiquitous environmental contaminants, occurring in most human adipose tissue and blood samples. It has recently been recognized that
PCBs and related compounds share important structural properties with
thyroid hormones and can bind
thyroid hormone binding proteins. It is reasonable that such specific binding interactions can modulate the distribution of these compounds in the body and alter
hormone-
protein interactions that are responsible for the maintenance of normal thyroid status. Most of the available evidence indicates that the levels of free
thyroid hormones in plasma are a reflection of the maintenance of normal thyroid status in any individual. A theoretical model for the transport of
thyroid hormones in blood has been extended to estimate the modulating effects of
PCBs on free
thyroid hormones. Using conservative assumptions based on experimental data, our calculations indicate that PCB concentrations normally found in humans can effect significant increases in free
thyroxine levels in serum by competing with serum
thyroid hormone binding proteins. Experimental data are discussed which support the proposal that antagonist binding of
PCBs to
thyroid hormone binding proteins in serum could produce varying degrees of
hypothyroidism. The
biological result is compatible with the "equilibrium hypothesis" in which
thyroid hormone redistributes between specific and nonspecific
binding proteins rather than emphasizing the importance of free
hormone as the active moiety.