Thyroid hormones
The thyroid hormones function via a well-studied set of nuclear receptors, termed the thyroid hormone receptors. These receptors, together with corepressor molecules, bind DNA regions called thyroid hormone response elements (TREs) near genes. This receptor-corepressor-DNA complex can block gene transcription. Triiodothyronine (T3), which is the active form of thyroxine(T4), goes on to bind to receptors. The deiodinase catalyzed reaction removes an iodine atom from the 5' position of the outer aromatic ring of Thyroxine's (T4) structure. When triiodothyronine (T3) binds a receptor, it induces a conformational change in the receptor, displacing the corepressor from the complex. This leads to recruitment of coactivator proteins and RNA polymerase, activating transcription of the gene.
Flame retardant
Many halogenated flame retardants with aromatic rings, including most brominated flame retardants, are likely thyroid hormone disruptors. The thyroid hormones triiodothyronine (T3) and thyroxine (T4) carry iodine atoms, another halogen, and are structurally similar to many aromatic halogenated flame retardants, including PCBs, TBBPA, and PBDEs. Such flame retardants therefore appear to compete for binding sites in the thyroid system, interfering with normal function of thyroid transport proteins (such as transthyretin) in vitro and thyroid hormone receptors. A 2009 "in vivo" animal study conducted by the US Environmental Protection Agency (EPA) demonstrated that deiodination, active transport, sulfation, and glucuronidation may be involved in disruption of thyroid homeostasis after perinatal exposure to PBDEs during critical developmental time points in utero and shortly after birth. Disruption of deiodinase as reported in the Szabo et al., 2009 "in vivo" study was supported in a follow-up "in vitro" study. The adverse effects on hepatic mechanism of thyroid hormone disruption during development have been shown to persist into adulthood. The EPA noted that PBDEs are particularly toxic to the developing brains of animals. Peer-reviewed studies have shown that even a single dose administered to mice during development of the brain can cause permanent changes in behavior, including hyperactivity.