Endocrine Abstracts

Thyroid hormone (T3) is essential for skeletal development and maintenance of bone mineralisation. T3 actions are mediated by two receptors, TRalpha and TRbeta. Mutations in TRbeta cause autosomal dominant resistance to thyroid hormone (RTH) due to dominant negative activity of the mutant receptor. Short stature and abnormal skeletal development are prominent features of RTH, whereas TRalpha mutations have not been described and are postulated to result in no phenotype or to b...

Thyroid hormone (T3) receptor beta (TRbeta) mutations cause resistance to thyroid hormones (RTH), characterised by decreased tissue sensitivity to T3. The TRbetaPV mutation (C-insertion at codon 448 leads to a frameshift of the carboxy-terminal 14 amino acids) was derived from a patient with severe RTH and generates a receptor lacking T3-binding and transactivation activities. Heterozygous mutant mice have a mildly impaired pituitary-thyroid axis; severe RTH and limb shortenin...