Searchable abstracts of presentations at key conferences in endocrinology

ea0019oc1 | Young Endocrinologist prize session | SFEBES2009

Winner of the British Thyroid Association Award

Galliford TM , Ghaffar A , Bassett JHD , Williams GR

T3 regulates bone development and its actions are mediated by TRα and TRβ. Using TR knockout mice we demonstrated that TRα1 is the predominant mediator of T3 action in bone, although TRα2 (a non-T3 binding isoform of unknown function) and TRβ1 are also expressed in the skeleton. We show that mice lacking TRα2 have characteristic skeletal abnormalities of delayed closure of the skull sutures, abnormal clavicle development and reduced bone mineraliz...

ea0011oc55 | Calcium and bone OC49 Novartis Oncology Young Investigator Award | ECE2006

Thyroid hormones stimulate osteoblast differentiation but inhibit mineralization of bone nodules in vitro

Williams AJ , Barnard JC , Bassett JHD , Williams GR

Thyroid hormones stimulate bone formation and linear growth in children. Paradoxically, childhood thyrotoxicosis causes short stature and craniosynostosis due to early closure of the growth plates and skull sutures. In adults, however, thyroid hormone excess increases bone turnover and results in progressive bone loss and osteoporosis. Activating mutations of fibroblast growth factor receptor-3 (FGFR3) cause achondroplastic dwarfism and we have shown that T3 augments FGFR sign...

ea0011oc51 | Calcium and bone OC49 Novartis Oncology Young Investigator Award | ECE2006

TSH receptor action in osteoblasts and osteoclasts in vitro

Murphy E , Williams AJ , Galliford TM , Costagliola S , Vassart G , Bassett JHD , Williams GR

Recent studies suggest TSH inhibits bone remodeling, indicating that TSH deficiency rather than thyroid hormone excess could cause bone loss in thyrotoxicosis. The findings predict that TSH receptor (TSHR) stimulating antibodies (TSHRAb) should inhibit bone turnover, whereas Graves’ disease patients exhibit high bone turnover with increased fracture susceptibility. We characterized TSH-action in primary human and mouse osteoblasts and osteoclasts, and explored whether a p...

ea0011oc54 | Calcium and bone OC49 Novartis Oncology Young Investigator Award | ECE2006

Adult mice harbouring a dominant negative R384C mutation of TRalpha1 have a marked increase in trabecular bone and micro-mineralisation density

Bassett JHD , Nordstrom K , Vennstrom B , Howell PGT , Boyde A , Williams GR

T3-receptor alpha (TRa) is the predominant TR isoform in bone. To investigate its function, we analysed mice harbouring a dominant negative R384C mutation in TRa1 (TRa1m/+). The homozygous TRa1m/m mutation is lethal whereas heterozygotes are euthyroid displaying only transient postnatal hypothyroidism. Critically, dominant negative activity of the mutation is overcome by a 10-fold increase in T3, which is achieved by crossing TRa1m/+ mutants wi...

ea0011p10 | Bone | ECE2006

Thyroid hormone receptor alpha has a critical negative role in maintenance of the adult skeleton

Bassett JHD , O’Shea PJ , Boyde A , Howell PGT , Samarut J , Chassande O , Williams GR

In developmental studies of mice lacking T3-receptor alpha (TRa0/0) and beta (TRb−/−) we demonstrated delayed endochondral ossification, reduced mineralisation and short stature in TRa0/0 mice, despite euthyroidism. In contrast, TRb−/− mice, which display thyroid hormone resistance with elevated T4 and T3 levels, have advanced ossification, increased mineralisation and accelerated growth. T3-target gene studie...

ea0011oc50 | Calcium and bone OC49 Novartis Oncology Young Investigator Award | ECE2006

Congenitally hypothyroid mice with (Pax8−/−) or without (hyt/hyt) functional TSH receptors (TSHR) display equivalent skeletal phenotypes

Williams GR , Swinhoe R , Murphy E , Williams AJ , Costagliola S , Vassart G , Howell PGT , Boyde A , Flamant F , Samarut J , Weiss R , Refetoff S , Bassett JHD

Studies of TSHR−/− mice suggest that TSH inhibits bone turnover, but these mice have congenital hypothyroidism and the actions of TSH cannot be separated from effects of thyroid hormone deficiency. We characterised skeletal development in hyt/hyt mice, which have a point mutation in the Tshr gene, and Pax8−/− mice with thyroid gland agenesis. Hyt/hyt mice have a 100-fold increase in TSH but inactive TSHRs, whereas Pax8&...