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Iodothyronine deiodinase enzyme activities in bone
Allan J Williams1, Helen Robson2, Monique H A Kester3
1Molecular Endocrinology Group, Division of Medicine and Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.
Bone
|May 13, 2008
Summary
Thyroid hormone transport via monocarboxylate transporter-8 (MCT8) and deiodinase activity in bone cells were investigated. D3 enzyme activity limits thyroid hormone availability in bone, impacting skeletal development.
Area of Science:
- Endocrinology
- Bone Biology
- Cellular Metabolism
Background:
- Euthyroid status is critical for skeletal development and maintenance.
- Mechanisms controlling thyroid hormone supply to bone cells are not fully understood.
- Thyroid hormone entry into cells occurs via monocarboxylate transporter-8 (MCT8).
Purpose of the Study:
- To investigate MCT8 expression in skeletal cells.
- To determine the presence and function of deiodinase enzymes (D1, D2, D3) in chondrocytes, osteoblasts, and osteoclasts.
- To elucidate thyroid hormone regulation in bone.
Main Methods:
- Gene expression analysis using RT-PCR.
- Measurement of D1, D2, and D3 enzyme activities.
- Primary cell cultures of chondrocytes, osteoblasts, and osteoclasts.
Main Results:
- MCT8 mRNA was detected in all skeletal cell types and differentiation stages.
- D1 activity was undetectable in all bone cells.
- D2 activity was found only in mature osteoblasts, while D3 activity was present throughout differentiation.
Conclusions:
- Skeletal T3 availability is likely limited by D3-mediated inactivation rather than MCT8 uptake or D2 production.
- D3 activity plays a significant role in regulating thyroid hormone levels in the developing and adult skeleton.
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