Triiodothyronine and breast cancer

Figure 1 Production and action of thyroid hormone. The key components required for thyroid hormone action are shown, demonstrated by a range of clinical observations. (1) Thyroid hormones (T4 and T3) are produced by the thyroid gland and are regulated by thyroid stimulating hormone (TSH) produced by the hypophysis, which is stimulated by thyrotropin-releasing hormone (TRH). Once released, T4 and T3 exert a negative feedback mechanism on the production of TRH and TSH; and (2) 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 rT3. Unliganded TR heterodimerizes with RXR and binds to a TRE and then to a corepressor, such as a nuclear receptor corepressor (NcoR); thus, repressing gene expression. T3 binding to the ligand-binding domain results in movement of the carboxyterminal helix 12, disruption of corepressor binding, and promotion of coactivator binding, which then leads to recruitment of polymerase III and the onset of gene transcription. Adapted from Ref.[13].