The iodothyronine deiodinases initiate or terminate
thyroid hormone action and therefore are critical for the biological effects mediated by
thyroid hormone. Over the years, research has focused on their role in preserving serum levels of the biologically active molecule T(3) during
iodine deficiency. More recently, a fascinating new role of these
enzymes has been unveiled. The activating
deiodinase (D2) and the inactivating
deiodinase (D3) can locally increase or decrease
thyroid hormone signaling in a tissue- and temporal-specific fashion, independent of changes in
thyroid hormone serum concentrations. This mechanism is particularly relevant because
deiodinase expression can be modulated by a wide variety of endogenous signaling molecules such as sonic hedgehog,
nuclear factor-kappaB,
growth factors,
bile acids,
hypoxia-inducible factor-1alpha, as well as a growing number of
xenobiotic substances. In light of these findings, it seems clear that deiodinases play a much broader role than once thought, with great ramifications for the control of
thyroid hormone signaling during vertebrate development and metamorphosis, as well as injury response, tissue repair, hypothalamic function, and energy homeostasis in adults.