Searchable abstracts of presentations at key conferences in endocrinology

ea0044pl8 | British Thyroid Association Pitt-Rivers Lecture | SFEBES2016

Thyroid hormone: far reaching consequences of local actions

Williams Graham

Thyroid hormone action in individual target tissues is a complex and tightly regulated process. Thyroid hormones (thyroxine, T4 and triiodothyronine, T3) enter target cells via active transport mediated by specific transporter proteins. T4 is a biologically inactive pro-hormone that is converted to the active hormone T3 by removal of a critical iodine atom. Two iodothyronine deiodinase enzymes (Dio2 and Dio3) are expressed in periphe...

ea0031s7.1 | Thyroid hormone receptors – mutations and implications (Supported by <emphasis role="italic">Journal of Molecular Endocrinology</emphasis>) | SFEBES2013

Physiologically distinct roles for thyroid hormone receptor isoforms

Williams Graham R

The majority of T3 actions are mediated by nuclear thyroid hormone receptors (TRα and TRβ), which act as hormone-inducible transcription factors. TRs are constitutively localised to the nucleus and, in the absence of hormone, bind to T3-response elements (TREs) located in the promoter regions of T3 target genes to mediate transcriptional repression. Entry of T3 to the nucleus and high affinity binding to TRs results in de-r...

ea0025pl6 | Society for Endocrinology Medal Lecture | SFEBES2011

The bare bones of thyroid hormones

Williams Graham R

Hypothyroidism delays bone formation, whilst thyrotoxicosis accelerates skeletal development but is a risk factor for osteoporosis. We characterized mice with mutation or deletion of T3 receptors, TRα and TRβ, in several genetic backgrounds. Delayed ossification and growth retardation were observed in TRα mutants, whereas TRβ mutants had advanced bone age. Adult TRα mutants had high bone mass, whereas TRβ mutants were osteoporotic. Targ...

ea0015s23 | Thyroid hormones in development: physiology and clinical implications | SFEBES2008

The HPT axis in control of skeletal development

Williams Graham R

Hypothyroidism delays bone development, whilst thyrotoxicosis causes osteoporosis. Recent studies have challenged understanding of skeletal responses to thyroid hormone by proposing TSH as a negative regulator of bone turnover and suggesting bone loss in hyperthyroidism results from TSH deficiency and not T3-excess. To investigate, we characterised mice with mutations or deletions of the genes encoding T3 receptor (TR) α and TRβ. Endochondral ossification was retarde...

ea0014s15.4 | Novel bone hormones and regulators | ECE2007

Thyroid hormones/TR and bone

R Williams Graham

Childhood hypothyroidism results in severely delayed skeletal development whereas adult thyrotoxicosis is associated with a 3–4 fold increase in osteoporotic fracture. To investigate molecular mechanisms underlying these abnormalities we characterized the skeletal phenotypes of mice harboring dominant negative mutations (TRα1PV/+, TRα1R384C/+, TRβPV/PV) or deletions (TRα0/0, TRβ−/−) of the genes encoding TRα and TRβ. Endochon...

ea0013p328 | Thyroid | SFEBES2007

T3 rather than TSH mediates the effects of altered thyroid status on bone turnover in man

Murphy Elaine , Williams Graham Richard

Recent controversial studies in mice imply that TSH inhibits bone remodelling, suggesting TSH-deficiency rather than thyroid hormone excess causes bone loss in thyrotoxicosis. Measurement of the TRH-stimulated rise in TSH following three days administration of graded doses of T3 is the gold-standard for determining resistance to thyroid hormone (RTH). During this test, T3 excess coupled with suppressed TSH should induce high bone turnover, whilst administration of TRH causes a...

ea0034oc4.4 | Thyroid and bone | SFEBES2014

Thyroid hormones stimulate osteoclastogenesis via TRα-dependent actions in osteoblasts

Logan John G , Bassett J H Duncan , Williams Graham R

Thyrotoxicosis results in osteoporosis and thyroid hormone (T3) stimulates osteoclastic bone resorption by unknown mechanisms. We previously demonstrated that knockout mice lacking thyroid hormone receptor α (TRα0/0) are euthyroid but have high bone mass, whereas mice lacking TRβ (TRβ−/−) are thyrotoxic and have osteoporosis. Tartrate resistant acid phosphatase (TRAcP) staining revealed osteoclast numbers were re...

ea0034p421 | Thyroid | SFEBES2014

Treatment with a TRα1 antagonist increases bone mineral content

Waung Julian A , Bassett J H Duncan , Williams Graham R

Thyroid hormones regulate adult bone turnover. Thyrotoxicosis results in high turnover osteoporosis whilst hypothyroidism leads to low bone turnover with increased bone mass and mineralisation. T3-target tissues express thyroid hormone receptor alpha (TRα), thyroid hormone receptor beta (TRβ)or both receptors. TRα1 mediates the actions of T3 in bone and in skeletal cells TRα1 mRNA expression is 12-fold higher than TRβ1. Accordingl...

ea0030oc1.4 | Oral Communications 1 | BSPED2012

Skeletal effects of hypothyroidism are mediated by thyroid hormone receptor α

Cheung Moira , Boyde Alan , Evans Holly , Bassett Duncan , Williams Graham

Childhood hypothyroidism results in delayed skeletal maturation and impaired growth. Thyroid hormones act via thyroid hormone receptors α (TRα) and TRβ which are tempo-spatially regulated. In the skeleton, TRα is the predominant receptor, thus we hypothesise that the skeletal effects of hypothyroidism are mediated by TRα. To investigate this we assessed the response of wild type (wt), TRα knockout (TRα0/0) and TRβ knockout (TR...