Received September 15, 2004
This article is principally intended to describe the facts concerning the actions of 3,5-diiodothyronine (T2). Until recent years, T2, because of its very low affinity for thyroid hormone receptors (THR), was considered an inactive metabolite of thyroid hormones (TH) (thyroxine (T4) and triiodo-L-thyronine (T3)). Several observations, however, led to a reconsideration of this idea. Early studies dealing with the biological activities of this iodothyronine revealed its ability to stimulate cellular/mitochondrial respiration by a nuclear-independent pathway. Mitochondria and bioenergetic mechanisms seem to be major targets of T2, although outside the mitochondria T2 also has effects on carriers, ion-exchangers, and enzymes. Recent studies suggest that T2 may also affect the transcription of some genes, but again the underlying mechanisms seem to be different from those actuated by T3. The accumulated evidence permits the conclusion that the actions of T2 do not simply mimic those of T3 but instead are specific actions exerted through mechanisms that are independent of those actuated by T3 and do not involve THR.
KEY WORDS: 3,5-diiodothyronine, mitochondria, energy metabolism, cytochrome c oxidase, iodothyronine, thyroid hormones