Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2007) 14 S14.3

ECE2007 Symposia Trojan horses for steroids (4 abstracts)

Hepatic deiodinase activity is dispensable for the maintenance of normal thyroid hormone levels in mice

Ulrich Schweizer

Charité Universitätsmedizin Berlin, Berlin, Germany.

The main product of the thyroid is thyroxine (T4). However, the physiological ligand of nuclear thyroid hormone receptors is triiodothyronine, T3. Deiodination of T4 to yield T3 is achieved by 5′-deiodinase activity. Type I-deiodinase (Dio1) was the first deiodinase cloned and its strong expression in liver and kidny, together with the size of these organs, suggested a role for Dio1 in peripheral conversion of T4 to T3. Later, Dio2 and Dio3 were cloned, enzymes with a more restricted pattern of expression that mediate 5′- and 5-deiodination, respectively. A model emerged in which activation and inactivation of thyroid hormones is governed by the concerted action of tissue-specific deiodinase expression. One aspect of this familiar textbook model, a central role of hepatic Dio1 in T3 production, was recently challenged. Since all deiodinase enzymes are selenoproteins, targeted removal of the gene encoding selenocysteine tRNA (Trsp) allowed the liver-specific inactivation of Dio1 activity. Using Albumin-Cre; Trsp fl/fl mice we showed that loss of hepatic deiodinase did not disturb circulating thyroid hormone levels. Moreover, deiodinase activities in other organs did not show compensatory up-regulation. Data derived from the conventional Dio1 knockout mice suggest that hepatic Dio1 is involved in the re-cycling of iodine from iodothyroines. Since the targeted inactivation of Dio2 perturbed pituitary feedback regulation, but did not reduce serum T3 levels, the question remains which deiodinase provides circulating T3. We have taken these investigations further and will present data regarding the effects of thyroid-specific Trsp inactivation in transgenic mice.

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