Endocrine Abstracts

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...

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...

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. ...

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...

Meningiomas are the most common intracranial tumors accounting for 20 to 30% of central nervous system tumors. Currently, only two risk factors have been highlighted: the history of exposure (therapeutic or accidental) to ionizing radiation, and some genetic predispositions syndromes in particular Neurofibromatosis type 2. Given the feminine predominance and the presence of progesterone receptors expression in meningiomas, authors began to focus on hormonal factors as a risk f...

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...

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...

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...

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&...