REVIEW: Biological Effects of 3,5-Diiodothyronine (T₂)

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F. Goglia

Dipartimento di Scienze Biologiche ed Ambientali-Universita degli Studi del Sannio-Via Port'Arsa, 11 82100 Benevento, Italy; fax: +39-082423013; E-mail: goglia@unisannio.it

Received September 15, 2004

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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.

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KEY WORDS: 3,5-diiodothyronine, mitochondria, energy metabolism, cytochrome c oxidase, iodothyronine, thyroid hormones

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