Searchable abstracts of presentations at key conferences in endocrinology

ea0011s14 | Thyroid and the heart | ECE2006

Role of thyroid hormone receptor isoforms in development and function of heart and other tissues

Samarut J

Thyroid hormone receptors are ligand dependant transcription factors. They mediate a genomic response initiated by the thyroid hormone triiodothyronine, T3.In mice and humans two isotypes, TRα and TRβ, are produced from two different genes, and several isoforms of each isotype are present in the tissues. The knock out of either TRα or TRβ genes induces different phenotypes and several studies led to the conclusion that the TRα re...

ea0007s4 | British Thyroid Association Pitt Rivers Lecture | BES2004

Are thyroid hormone receptors good or bad for you?

Samarut J

Thyroid hormone (T3) works through nuclear receptors which are encoded by two genes TRalpha and TRbeta. Each gene encodes several isoforms among which some are not true receptors as they do not bind to DNA or do not bind thyroid hormone. In the absence of T3, thyroid hormone the receptors (apo-receptors) behave as transcription repressors toward target genes. Upon binding the hormone, the apo-receptors are transformed into holo-receptors which work as tanscription activators. ...

ea0007s4biog | British Thyroid Association Pitt Rivers Lecture | BES2004

British Thyroid Association Pitt Rivers Lecture

Samarut J

Jacques Samarut, Ecole Normale Superieure de Lyon, Université Claude Bernard Lyon, Hospices Civils de Lyon, France Abstract I graduated at the University of Lyon in 1981 working on the development of hematopoiesis in chick embryo. At the same time I started working on retrovirus oncogenes and their transformation of hematopoietic progenitor cells. I then moved to the Rockefeller University (New York) in the Lab...

ea0004s6 | Novel aspects of thyroid diseases | SFE2002

Specific roles of thyroid hormone receptor isoforms during development of the mouse

Samarut J

Thyroid hormone T3 controls many functions in Vertebrates including developmental processes (body and skeletal growth, nervous system maturation) and physiological regulations (heart rate, thermogenesis, glycemia, T3 production). The action of T3 is mediated by two isotypes of nuclear receptors, respectively TRa and TRb that are encoded by two different genes. Each of these two genes encodes several isoforms, several of which are not true receptors.T3 is...

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...

ea0009p149 | Thyroid | BES2005

Thyroid hormone (T3) activates GH/IGF-1 signalling during skeletal development

O'Shea P , Sriskantharajah S , Yao H , Suzuki H , Cheng S , Chassande O , Samarut J , Williams G

T3, GH and IGF-1 are essential for skeletal development. GH acts directly on growth plate chondrocytes and also via a local paracrine pathway involving IGF-1, but it is unclear whether T3 stimulates bone formation directly or indirectly. To address this, we determined expression of GH-receptor, IGF-1 and IGF-1 receptor (IGF-1R) by in situ hybridisation and activation of downstream STAT5 and AKT signalling by immunohistochemistry in growth plates from four T3-receptor (TR) muta...

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...

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&...