Searchable abstracts of presentations at key conferences in endocrinology

ea0010s9 | Non classical sites of action of classical hormones | SFE2005

Rapid actions of steroids via non-classical receptors

Williams G

A variety of rapid responses to steroid hormones have been identified during the last decade. In contrast to classical actions mediated via nuclear receptors with a time lag of hours, rapid actions occur within seconds or minutes via second messenger signalling cascades. Classical genomic actions are well-defined and sensitive to transcription and protein synthesis inhibitors. Steroid hormones enter the cell by diffusion or via transport proteins and bind to cognate receptors ...

ea0010s36 | Endocrinology of bone diseases: recent clinical and basic developments | SFE2005

Thyroid and bone

Williams G

Thyroid hormones are essential for skeletal development and bone maintenance. Childhood hypothyroidism causes growth arrest with delayed bone maturation, whereas thyrotoxicosis accelerates growth and advances bone age. In adults, thyrotoxicosis causes osteoporosis and increased susceptibility to fracture. To investigate mechanisms of T3 action in bone, we analyzed T3 receptor (TR) mutant mice. TRα-null (TRα0/0) mice are euthyroid but display delayed ossification with...

ea0004s5 | Novel aspects of thyroid diseases | SFE2002

Thyroid hormone actions on bone and growth

Williams G

Thyroid hormone (T3) is required for skeletal development during childhood and T3 regulates bone turnover and mineralisation in adults. Thyrotoxicosis is an established risk factor for osteoporosis. We and others have shown that T3 receptors (TRs) are expressed in osteoblasts and growth plate chondrocytes, which represent primary T3-target cells in the skeleton. T3 effects on osteoclast-mediated bone resorption are thought to be mediated by osteoblasts via paracrine pathways. ...

ea0026s22.1 | Non traditional effects of pituitary hormones | ECE2011

Non-thyroidal effects of TSH

Williams G R

The glycoprotein hormone, TSH, is synthesized and secreted by thyrotrophs in the anterior pituitary gland. It acts at the TSH receptor (TSHR), a 7-transmembrane G-protein coupled cell membrane receptor expressed in thyroid follicular cells. The TSHR, thus, plays a key role in the regulation of thyroid status and growth of the thyroid gland. In recent years TSHR expression has also been identified in a wide variety of extra-thyroidal tissues including: anterior pituitary; hypot...

ea0025pl6biog | Society for Endocrinology Medal Lecture | SFEBES2011

Society for Endocrinology Medal Lecture

Williams G R

G R Williams, Imperial College London, London, UK. AbstractGraham R Williams obtained a BSc in Anatomy and MBBS from St Thomas’s Hospital, London and undertook PhD studies in Molecular Endocrinology at Birmingham University. He trained as a Howard Hughes and MRC Fellow at Harvard Medical School, USA and was an MRC Clinician Scientist Fellow in Birmingham. He was appointed Senior Lecturer at the Royal Postgraduate...

ea0019s39 | Novel aspects of bone physiology in relation to osteoporosis treatment | SFEBES2009

AMEND Young Investigators Award

Williams G R

Osteoporosis is characterised by bone fragility with increased susceptibility to fracture. The burden of osteoporosis already costs the NHS over £1.7 billion per annum but its prevalence is increasing. The skeleton is continually remodelled in response to endocrine, paracrine and mechanical signals by the coupled activities of osteoclasts and osteoblasts. Nevertheless, the continuous process of bone turnover results in an inexorable loss of bone because osteoblast-mediate...

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...

ea0012p134 | Thyroid | SFE2006

MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) and thyrotoxicosis

Caputo C , Devendra D , Williams G , Dornhurst A

A 26-year-old woman presented with vomiting and cortical blindness. CT scan of the brain confirmed a right-sided parietal-occipital infarct, She subsequently developed seizures and neurological extension resulting in global dysphasia. Serum and CSF lactate were elevated (4.4 and 4.3 mmol/l respectively, NR<1.8). MELAS syndrome was confirmed by mitochondrial DNA analysis, which revealed an A3243G mutation in muscle and serum (85% muscle, 63% urinary epithelial cells and 33%...

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. ...

ea0007p31 | Cytokines and growth factors | BES2004

Thyroid hormone regulates heparan sulphate proteoglycans in the growth plate

Bassett J , Swinhoe R , Williams G

T3 is essential for normal skeletal development. Childhood hypothyroidism causes delayed bone formation, whereas T3-excess accelerates growth and epiphyseal closure. Fibroblast growth factors (FGFs) act via receptor tyrosine kinases (FGFRs) to inhibit chondrocyte proliferation, matrix production and skeletal maturation. Dimerisation of FGFRs and their functional interaction with FGFs requires heparan sulphate proteoglycans (HSPGs). We recently showed that T3 induces FGFR-1 exp...