3, 5-Diiodothyronine: Biological Actions and Therapeutic Perspectives

The purpose of this review is to summarize the current state of knowledge concerning the biological activities of 3, 5-diiodothyronine (T 2) and its potential use as a pharmacological agent. Until recent years, T2 was considered an inactive metabolite of thyroid hormones 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, essentially by a nuclear-independent pathway. Mitochondria and the energytransduction apparatus 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 T 2 may also affect the transcription of some genes, but again the underlying mechanisms seem to differ 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 thyroid hormone receptors. In addition, very recent evidence leads us to suggest that T2 may be a potentially useful agent for the treatment of diet-dependent overweight (and the consequent hypertriglyceridemia and high cholesterol level) without inducing thyrotoxicosis.