T-Time again – The diversity of actions of thyroid hormones (TH), their aminergic (TAM) and acetic acid (TAc) metabolites

Abstract

The thyroid gland produces the iodine containing thyroid hormones (TH) T4 and T3. Three essential trace elements, iodine, selenium and iron are required for TH biosynthesis. The synthesis, storage and secretion of TH occur in the lumen of the angiofollicular units, a polarized epithelial monolayer of thyrocytes surrounded by a microcapillary network. A complex sequence of biochemical reactions, organized as “thyrosome” at the apical surface of thyrocytes, includes the multifunctional hemoprotein thyroid peroxidase (TPO) and utilizes thyroglobulin as the synthesis and storage protein for TH. The pituitary hormone thyrotropin regulates thyroid growth and angiofollicular function via its G-protein coupled receptor. Several benign and malignant disorders caused by dysfunction of individual components of this complex machinery have been identified. T4 replacement is a safe and well established effective treatment of hypothyroidism and hyperthyroidism can be treated by antithyroid drugs. Thyroid cancer is treated by radioiodine therapy, surgery or novel drugs targeting aberrant activated kinase signaling pathways or angiogenesis. Nutritional iodine deficiency impairs thyroid function and leads to goiter formation. Various nutritional and environmental agents including endocrine disrupting compounds, such as perchlorate, PCB 126, BPA, Hexabromocyclododecanes (HBCDs) and organochlorine compounds, also exert goitrogenic effects. Two types of autoimmune reactions target the thyroid gland. Both require treatment either with T4 replacement (hypothyroidism resulting from autoimmune thyroiditis) or antithyroid drugs, surgery or radioiodine (hyperthyroidism caused by Graves’ disease).