Impact of PCBs on thyroid hormone directed brain development

Thyroid hormones regulate neuronal proliferation, migration, process outgrowth, synaptic development and myelin formation in specific brain regions. Because brain development occurs during discrete windows of time, inappropriate levels of thyroid hormones in definitive periods can produce permanent damage, the nature of which depends upon the timing and magnitude of the insult. Thyroid hormones cross the placenta and enter the brain primarily as thyroxine (T-4); therefore, conditions selectively lowering serum T-4 levels alter brain hormone availability. Triiodothyronine (T-3) is the predominant form of the hormone that binds to the receptor. T-3 is produced from T-4 in the brain by the enzyme type II, 5'-deiodinase. Polychlorinated biphenyls (PCBs) are synthetic environmental toxicants that bear a striking structural resemblance to the active thyroid hormones and can, depending upon the species, dosage, and congener used act as agonists, antagonists, and partial agonists to thyroid hormones.