Endocrine Abstracts

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...

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...

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&...