In a seemingly wasteful fashion, the thyroid gland focuses its effort into secreting an inactive version of thyroid hormone T4. In fact, a hormone, from the Greek word for impulse, is a biologically active molecule, so in the case of thyroid hormone, the actual active hormone is that of the triply iodinated derivative, T3 . To successfully produce T3 , the human thyroid processes about 1000 nmol iodide daily, packaging the iodide into a very large molecule [thyroglobulin (Tg)] that is subsequently hydro- lyzed. The resulting iodinated products are sequentially un- leashed in a controlled manner so that, eventually, only 10 nmol of the highly potent T3 are secreted. The bulk of T3 production (40 nmol), however, occurs outside of the thyroid parenchyma through the conversion of T4 to T3 by the activating deiodinases, a group of selenoenzymes that can selectively remove iodine moi- eties from T4 (reviewed in Ref 1). Given that only 10 nmol or less of T3 are directly secreted from the thyroid, one would assume that an absence of the deiodinases should impair the overall daily production of T3, leading to systemic hypothyroidism. In this issue of Endocrinology, Galton et al. (2) challenge the conven- tional paradigm of thyroid hormone homeostasis by showing that mice lacking both of the activating deiodinases do just fine, because they are still capable of maintaining normal amounts of T3 in serum and do not suffer from systemic hypothyroidism.
Triumphs of the Thyroid Despite Lesser Conversion.
Jessica A. Hall and Antonio C. Bianco.Endocrinology, June 2009; doi:10.1210/en.2009-0347