Thyrostimulin and TSH are Novel Skeletal Paracrine Factors that Regulate Bone Turnover

Dr John Howard Duncan Bassett and Professor Graham Richard Williams, Molecular Endocrinology Group, Hammersmith Hospital, London

FINAL REPORT

Recent studies have suggested that in thyrotoxicosis a lack of thyroid stimulating hormone (TSH) as well as the excess of thyroid hormone may negatively affect bone structure and density. With the help of the 2004 British Thyroid Foundation Research Award we have been able to demonstrate that the thyroid stimulating hormone receptor (TSHR) but not TSH itself is found in skeletal cells. Furthermore, we have also demonstrated the presence of thyrostimulin in the same bone cells. Thyrostimulin is a recently identified new and alternative agonist that binds to the TSHR with high affinity. Our observation suggests the possibility of a novel local thyrostimulin/TSHR signalling pathway in the skeleton.

Despite this advance, treatment of bone cells with TSH or TSHR stimulating antibodies did not result in normal TSHR signalling suggesting an alternative pathway may be use in bone cells. A second series of experiments have suggested that although TSH/thyrostimulin/TSHR may have a minor role in skeletal regulation it is thyroid hormone and the thyroid hormone receptors that have the major role in regulation of skeletal development and the maintenance of adult bone.

These studies have already been presented at the 7th International Workshop on Resistance to Thyroid Hormone in Lyon, France and we were awarded the prize for the best submitted abstract and presentation. In addition, the work will be presented in two sessions at the 8th European Congress of Endocrinology in Glasgow 2006. This work forms the basis for a strong application for further research funding and will be submitted for publication in the near future. Research into this new field, which aims to gain new insights into how thyroid hormone affects bone turnover, would not have been possible without the generous support of the BTF and we are very grateful for your support. We are hopeful that these studies will pave the way for new approaches to prevent bone loss in thyroid patients exposed to and excess of thyroid hormone.