Think globally: act locally. New insights into the local regulation of thyroid hormone availability challenge long accepted dogmas

Recent evidence derived from transgenic mouse models and findings in humans with mutations affecting thyroid hormone (TH) metabolism have convincingly supported a model of TH signalling in which regulated local adjustment of active TH concentrations is far more important than circulating plasma horm...

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Bibliographic Details
Published in:Molecular and cellular endocrinology 2008-07, Vol.289 (1-2), p.1-9
Main Authors: Schweizer, Ulrich, Weitzel, Joachim M, Schomburg, Lutz
Format: Article
Language:English
Subjects:
Animals
Biological Transport
Brain - metabolism
Humans
Iodide Peroxidase - genetics
Iodide Peroxidase - metabolism
Mice
Mice, Knockout
Mice, Transgenic
Models, Biological
Signal Transduction
Thyroid Gland - metabolism
Thyroid Hormone Resistance Syndrome - metabolism
Thyroid Hormones - genetics
Thyroid Hormones - metabolism
Triiodothyronine - metabolism
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Summary:Recent evidence derived from transgenic mouse models and findings in humans with mutations affecting thyroid hormone (TH) metabolism have convincingly supported a model of TH signalling in which regulated local adjustment of active TH concentrations is far more important than circulating plasma hormone levels. Although this theory was put forward several years ago and has been supported by significant, but inherently indirect evidence, recent insights from targeted deletion of the genes encoding deiodinase (Dio) isozymes have revived this model and greatly increased our understanding of TH metabolism. However, gene targeting proved to be a double edged sword, since the overall model was supported, but several predictions are apparently not consistent with the new experimental evidence. Human genetics further provided additional exciting data on the physiological role of Dio isozymes that need to be incorporated into any model of TH biology. The recent identification of mutations in the T3 plasma membrane transporter MCT8 has sparked new interest in the role of TH in brain function, since affected patients suffered from psychomotor retardation. Moreover, selenium (Se) and TH physiology have finally been unequivocally connected by newly identified inherited defects in a gene involved in selenoprotein biosynthesis. Finally, a link between Dio expression and energy metabolism has been delineated in mice that may hold great promise for the management of the adiposity pandemic.
ISSN:0303-7207
0303-7207
DOI:10.1016/j.mce.2008.04.007