Authors
Williams, Allan JRobson, Helen
Kester, Monique H A
Van Leeuwen, Johannes P T M
Shalet, Stephen M
Visser, Theo J
Williams, Graham R
Affiliation
Molecular Endocrinology Group, Division of Medicine and Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.Issue Date
2008-07
Metadata
Show full item recordAbstract
Euthyroid status is essential for normal skeletal development and maintenance of the adult skeleton, but the mechanisms which control supply of thyroid hormone to bone cells are poorly understood. Thyroid hormones enter target cells via monocarboxylate transporter-8 (MCT8), which provides a functional link between thyroid hormone uptake and metabolism in the regulation of T3-action but has not been investigated in bone. Most circulating active thyroid hormone (T3) is derived from outer ring deiodination of thyroxine (T4) mediated by the type 1 deiodinase enzyme (D1). The D2 isozyme regulates intra-cellular T3 supply and determines saturation of the nuclear T3-receptor (TR), whereas a third enzyme (D3) inactivates T4 and T3 to prevent hormone availability and reduce TR-saturation. The aim of this study was to determine whether MCT8 is expressed in the skeleton and whether chondrocytes, osteoblasts and osteoclasts express functional deiodinases. Gene expression was analyzed by RT-PCR and D1, D2 and D3 function by sensitive and highly specific determination of enzyme activities. MCT8 mRNA was expressed in chondrocytes, osteoblasts and osteoclasts at all stages of cell differentiation. D1 activity was undetectable in all cell types, D2 activity was only present in mature osteoblasts whereas D3 activity was evident throughout chondrocyte, osteoblast and osteoclast differentiation in primary cell cultures. These data suggest that T3 availability especially during skeletal development may be limited by D3-mediated catabolism rather than by MCT8 mediated cellular uptake or D2-dependent T3 production.Citation
Iodothyronine deiodinase enzyme activities in bone. 2008, 43 (1):126-34 BoneJournal
BoneDOI
10.1016/j.bone.2008.03.019PubMed ID
18468505Type
ArticleLanguage
enISSN
8756-3282ae974a485f413a2113503eed53cd6c53
10.1016/j.bone.2008.03.019
Scopus Count
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