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 triiodothyronine (T3) 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, independently of changes in thyroid hormone
serum concentrations. This mechanism is particularly relevant as deiodinase expression
can be modulated by a wide variety of endogenous signaling molecules such as sonic
hedgehog, NF-kappaB, growth factors, bile acids, HIF-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.
