Fig. 1. Chemicals can interfere with thyroid hormone action at several points. (A) The pituitary gland and hypothalamus regulate thyroid hormone synthesis through thyroid-stimulating hormone (TSH) release. (B) Thyroid hormone is synthesized in the thyroid gland. If TSH stimulates thyrocytes, iodine uptake via the sodium iodide symporter (NIS), thyroglobulin (Tg) production, and oxidation by thyroid peroxidase (TPO) occur. (C) Thyroid hormone is carried on binding proteins such as thyroxine-binding globulin (TBG) and transthyretin (TTR). (D) Thyroid hormone is metabolized in the liver by deiodinase (DIO), UDP-glucuronosyltransferase (UGT), or sulfotransferase (SULT) and eliminated in bile. (E) Thyroid hormone binds to the thyroid hormone receptor (TR) in target cells and activates thyroid hormone signaling pathways. T₄, thyroxine; T₃, triiodothyronine.