Searchable abstracts of presentations at key conferences in endocrinology

ea0005p254 | Thyroid | BES2003

Thyroid hormone receptor (TR) activity is modulated by TRdeltabeta3 in a cell-, response element-, and TR isoform-specific manner

Harvey C , Williams G

Alternative splicing of the rat THRB gene produces thyroid hormone (T3) receptor (TR) beta isoforms 1-3 and also TRdeltabeta3, which lacks the DNA binding domain but binds T3. TRbeta1 is ubiquitous; TRbeta2 is found predominantly in pituitary and hypothalamus, whilst TRbeta3 and TRdeltabeta3 are expressed widely in a ratio that is tissue-specific and T3-dependent. We investigated the function of the newly identified TRbeta3 and TRdeltabeta3 isoforms by transient transfection a...

ea0007oc17 | Thyroid | BES2004

Thyroid hormone (T3) activates fibroblast growth factor (FGF) receptor signalling in bone

Barnard J , Williams A , Harvey C , Williams G

FGFs and T3 are required for skeletal development. Activating mutations of FGF receptor-1 (FGFR-1) and FGFR-2 cause craniosynostosis, whilst FGFR-3 is a negative regulator of chondrocyte proliferation and activating mutations cause achondroplasia. Childhood hypothyroidism causes delayed ossification and growth retardation, whereas thyrotoxicosis accelerates bone development, induces premature growth plate and skull suture closure and causes short stature and craniosynostosis. ...

ea0005p7 | Bone | BES2003

Effects of thyroid hormone (T3) on fibroblast growth factor signalling in bone

Barnard J , Williams A , Harvey C , Williams G

T3 and fibroblast growth factors (FGFs) are critical regulators of chondrocyte proliferation during bone formation and we identified recently that T3 modulates skeletal FGF receptor-1 (FGFR1) activity. FGFRs signal via several routes including mitogen-activated protein kinase (MAPK), STAT and phospholipase C gamma pathways. Mechanisms determining which pathways are activated by FGFRs are poorly understood but include alternative splicing of exons encoding variable domains with...

ea0005oc35 | Thyroid and Calcium | BES2003

Five human thyroid hormone receptor beta1 5'-UTR isoforms differentially regulate levels of gene expression and protein translation in individual tissues

Frankton S , Gleason L , Harvey C , Williams G

In humans only thyroid hormone (T3) receptor (TR) beta1 and beta2 mRNAs have been identified, whereas alternative splicing generates recently characterised beta3 and deltabeta3 transcripts in rat and further N-terminal isoforms in other species. We investigated whether additional transcripts arise from the human TRbeta gene by 5'-RACE. Five distinct TRbeta1 transcripts were isolated, including the previously described TRbeta1 mRNA and four novel 5'-untranslated region (5'-UTR)...

ea0005oc33 | Thyroid and Calcium | BES2003

Contrasting skeletal phenotypes in mice with an identical mutation targeted to either the TRalpha or TRbeta gene

O'Shea P , Harvey C , Suzuki H , Kaneshige M , Kaneshige K , #S-y|#Cheng|# , Williams G

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...

ea0003oc19 | Growth Regulation | BES2002

Thyroid hormone activates fibroblast growth factor receptor-1 in bone

Scott A , Harvey C , O'Shea P , Stevens D , Samarut J , Chassande O , Williams G

Although thyroid hormone (T3) and the T3-receptor (TR) alpha gene are essential for skeletal development, T3-signalling pathways in bone have not been characterised. We identified fibroblast growth factor receptor-1 (FGFR1) as a novel T3-inducible gene in osteoblasts by subtraction hybridisation. FGFR1 mRNA was induced 2-3 fold in osteosarcoma cells and primary cultured osteoblasts treated with T3 (0.1-1000nM, 0-48h) and FGFR1 protein was stimulated 2-4 fold over the same peri...

ea0003oc20 | Growth Regulation | BES2002

Advanced bone formation in mice with resistance to thyroid hormone due to a targeted mutation in the thyroid hormone receptor beta gene

O'Shea P , Harvey C , Suzuki H , Kaneshige M , Kaneshige K , #S-y|#Cheng|# , Williams G

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...