2.50
Hdl Handle:
http://hdl.handle.net/10541/58680
Title:
Iodothyronine deiodinase enzyme activities in bone.
Authors:
Williams, Allan J; Robson, Helen; Kester, Monique H A; Van Leeuwen, Johannes P T M; Shalet, Stephen M; Visser, Theo J; Williams, Graham R
Abstract:
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.
Affiliation:
Molecular Endocrinology Group, Division of Medicine and Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.
Citation:
Iodothyronine deiodinase enzyme activities in bone. 2008, 43 (1):126-34 Bone
Journal:
Bone
Issue Date:
Jul-2008
URI:
http://hdl.handle.net/10541/58680
DOI:
10.1016/j.bone.2008.03.019
PubMed ID:
18468505
Type:
Article
Language:
en
ISSN:
8756-3282
Appears in Collections:
All Christie Publications ; Endocrinology

Full metadata record

DC FieldValue Language
dc.contributor.authorWilliams, Allan J-
dc.contributor.authorRobson, Helen-
dc.contributor.authorKester, Monique H A-
dc.contributor.authorVan Leeuwen, Johannes P T M-
dc.contributor.authorShalet, Stephen M-
dc.contributor.authorVisser, Theo J-
dc.contributor.authorWilliams, Graham R-
dc.date.accessioned2009-04-01T23:05:10Z-
dc.date.available2009-04-01T23:05:10Z-
dc.date.issued2008-07-
dc.identifier.citationIodothyronine deiodinase enzyme activities in bone. 2008, 43 (1):126-34 Boneen
dc.identifier.issn8756-3282-
dc.identifier.pmid18468505-
dc.identifier.doi10.1016/j.bone.2008.03.019-
dc.identifier.urihttp://hdl.handle.net/10541/58680-
dc.description.abstractEuthyroid 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.en
dc.language.isoenen
dc.subjectThyroid Hormone Metabolismen
dc.subjectMCT8en
dc.subjectChondrocyteen
dc.subjectOsteoblasten
dc.subjectOsteoclasten
dc.subject.meshAnimals-
dc.subject.meshBone and Bones-
dc.subject.meshFemale-
dc.subject.meshIodide Peroxidase-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshMice, Inbred Strains-
dc.subject.meshRats-
dc.subject.meshRats, Inbred Strains-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.titleIodothyronine deiodinase enzyme activities in bone.en
dc.typeArticleen
dc.contributor.departmentMolecular Endocrinology Group, Division of Medicine and Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.en
dc.identifier.journalBoneen
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