PCBS AND CIRCULATING THYROID HORMONE Experimental Animals

Polychlorinated biphenyls (PCBs) are well known to reduce the concentrations of thyroid hormones in the circulation of experimental animals (Bastomsky et al., 1976; Brouwer et al., 1998). Moreover, circulating levels of PCBs have been reported to co-vary with various measures of thyroid status in humans (Koopman-Esseboom et al., 1997; Osius et al., 1999). These observations form the basis for the hypothesis that PCBs disrupt thyroid hormone action by reducing circulating levels of thyroid hormone. This hypothesis is particularly important to explore because thyroid hormone is known to be essential in brain development and because PCB contamination is enormously widespread. Therefore, it is possible that PCBs may lead to neurological abnormalities in humans and animals by interfering with thyroid hormone action. Linking the known effects of PCB contamination on neurological development to disruption of thyroid hormone action is difficult for two basic reasons. First, there are many gaps in our understanding of the interaction of PCBs with the thyroid signaling system. Therefore, it is difficult to predict how PCBs may interfere with thyroid hormone action. Second, there are many gaps in our understanding of the mechanisms by which thyroid hormone acts during development. Therefore, it is difficult to determine whether the neurological effects of PCB exposure are similar to those effects predicted by the hypothesis of thyroid disruption. The goal of this review is to frame what is known about the interaction of PCBs with the thyroid system within the context of what is known about the mechanism of thyroid hormone action on brain development. The emphasis will be on PCB disruption of thyroid hormone action as opposed to thyroid function.