TTR and endocrine disruptors

Abstract

In Endocrine disruptors addition to binding thyroid hormones (THs), its endogenous ligands, transthyretin (TTR) can bind a large number of chemicals, including flavonoids, nonsteroidal anti-inflammatory drugs (NSAIDs), and environmental pollutants. By binding to TTR, these chemicals have the potential to change TH homeostasis in plasma and interfere with the thyroid system, particularly in rodents and lower vertebrates. A structure-activity relationship of those chemicals that compete with TH for binding to TTR was found for several groups of chemicals. Owing to the binding specificity of these chemicals for TTR, a competitive binding assay for TH binding to TTR has been used to detect potent TH-disrupting chemicals in samples obtained from various environments. Recent advances in pharmacological and physiological research indicate that some chemicals that bind to TTR may have a chemotherapeutically beneficial effect on TTR-mediated amyloid fibril formation, whereas other chemicals that bind to TTR may have an adverse effect on retinoid homeostasis. Possible roles for the binding of chemicals to TTR are discussed. © 2009 Springer-Verlag Berlin Heidelberg.