Disruptive Effect of Organotin on Thyroid Gland Function Might Contribute to Hypothyroidism

Figure 1

Production and action of thyroid hormones (TH) and a tentative representation of TBT disruption. The key components required for thyroid hormone action and possible TBT disruption are shown. (a) TH (T4 and T3) are produced by the thyroid gland and are regulated by thyroid-stimulating hormones (TSHs) produced by the hypophysis, which are stimulated by the thyrotropin-releasing hormones (TRHs). Once released, T4 and T3 exert a negative feedback mechanism on the production of TRH and TSH. TBT’s disruptive effect on the hypothalamic-pituitary-thyroid (HPT) axis with stimulation of TSH or gland inhibition function and (b) the effects of T4 in vivo are mediated via T3; T4 is converted to T3 in target tissues by deiodinases 1 and 2 (D1 and D2). Deiodinase 3 (D3) converts T3 to the inactive T3 (rT3). T3 binding to the TR heterodimerizes with type retinoid X receptors (RXR) and binds to a TH response element (TRE), disrupting the corepressor binding and promoting the coactivator binding, which then leads to recruitment of polymerase III and the onset of gene transcription (mRNA). TBT’s disruptive effect on thyroid in metabolic effect of T3 (inhibition) and T4 (diminished or incresead, if D2 is inhibited by TBT), with inhibition of deiodinases and TR or nonspecific linkage to TR.