Endocrine Abstracts

The complexity of thyroid hormone (TH) signaling pathways presents a myriad of targets for potential interference by environmental contaminants. Many of these sites of action can be detected by alterations in T3 and T4 concentrations in the blood. Iodine is essential for production of TH, severe deficiencies leading to hypothyroidism. Given the importance of TH in brain development, maintaining iodine status is especially critical during pregnancy - pregnant women with iodine deficiency (ID) and their progeny may be particularly susceptible to environmental exposures that impact the TH system. In this presentation, a rodent pregnancy model on perchlorate, an environmental contaminant that interferes with the iodine transport, and iopanoic acid (IOP), a chemical that interferes with TH metabolism will be described. Perchlorate, when combined with dietary ID induces structural defects in developing brain, alters synaptic transmission, and impairs behavioral measures of sensory gating. Reductions in serum TH in the fetus that persist to the first week of life are required to induce these changes, changes that were greatly exacerbated under conditions of ID. Decreases in serum TH induced by perchlorate stand in stark contrast to increases in serum T4 observed in response to exposure to IOP. IOP blocks deiodinases, enzymes responsible for activating and deactivating TH and maintain optimal receptor-level concentrations for T3-mediated gene transcription. Despite a peripheral state of hyperthyroidism, brain T3 is reduced in the newborn pup and a neuroanatomical defect similar to that reported for perchlorate was present in the brains of offspring. Together, the dissociation of peripheral vs central TH effects by IOP demonstrate the criticality of tissue levels TH while the combined effects of perchlorate and ID underscore the need to consider additional environmental stressors when determining the impact of chemical exposure on brain function. Does not reflect EPA policy.