Searchable abstracts of presentations at key conferences in endocrinology

ea0025s6.1 | Novel application of thyroid hormone analogues: thyroid hormones, thinking outside the capsule | SFEBES2011

Thyroid hormone action: genomic and non-genomic effects

Bassett J H Duncan

The classical genomic actions of triiodothyronine (T3) are mediated by high-affinity nuclear receptors that directly regulate gene expression. By contrast, the non-genomic effects of thyroid hormones occur rapidly and are unaffected by inhibitors of transcription and protein synthesis. The genomic actions of thyroid hormone have an established role in the development, differentiation and homeostatic maintenance of target tissues. The THRA and THRB gene...

ea0022s3.3 | Bone cell biology | ECE2010

The role of the hypothalamic–pituitary–thyroid axis in bone

Bassett J H Duncan

Disruption of the HPT-axis during growth profoundly influences skeletal development and effects may not be reversed fully following correction of thyroid status. Adult thyrotoxicosis leads to increased bone turnover and is an established risk factor for osteoporotic fracture. The conventional view that skeletal responses to abnormal thyroid status result solely from altered T3 action in bone has, however, been questioned by studies proposing TSH as a negative regula...

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...

ea0025p339 | Thyroid | SFEBES2011

Thyroid hormone receptor alpha is a permissive factor that regulates osteoclastogenesis indirectly

Nicholls Jonathan J , Combs Charlotte E , Williams Graham R , Bassett J H Duncan

Thyrotoxicosis is characterised by increased osteoclast activity. Thyroid hormone receptor alpha (TRα) is the predominant TR-isoform in bone and mice lacking TRα have skeletal hypothyroidism with impaired osteoclastic bone resorption. By contrast, mice lacking TRβ have skeletal hyperthyroidism and increased bone resorption. Thus, we hypothesized that T3 acts via TRα to stimulate osteoclastogenesis. Osteoclasts were differentiated in vitro ...

ea0034oc4.3 | Thyroid and bone | SFEBES2014

TRα mutation causes a severe and thyroxine-resistant skeletal dysplasia

Bassett J H Duncan , Boyde Alan , Zikmund Tomas , Evans Holly , Croucher Peter I , Zhu Xuguang , Park Jeong Won , Cheng Sheue-yann , Williams Graham R

A new genetic disorder has recently been identified that results from mutation of THRA, encoding thyroid hormone receptor α1 (TRα1). Affected children have a high serum T3:T4 ratio, constipation and a variable intellectual deficit, but exhibit a consistently severe skeletal dysplasia. Similar to these patients, Thra1PV/+ mice harbour a mutation that disrupts the C-terminal α-helix of TRα1 and express a domi...

ea0025p8 | Bone | SFEBES2011

Thyrostimulin expression and signalling in the skeleton

Bassett J H Duncan , Hernandez Rebecca , Combs Charlotte , Spek Anne van der , Yu Ming , Williams Allan , Murphy Elaine , Boyde Alan , van Zeijl Clementine J J , Boelen Anita , Williams Graham R

Hypothyroidism and thyrotoxicosis have detrimental effects on skeletal development and adult bone strength. These effects result from thyroid hormone actions in bone, although a direct role for TSH in osteoblasts and osteoclasts was postulated following analysis of TSH receptor (TSHR) null mice. This hypothesis remains controversial as other studies failed to demonstrate osteoblast or osteoclast responses to TSH in vitro. Thyrostimulin is a heterodimeric glycoprotein ho...

ea0031p352 | Thyroid | SFEBES2013

Local regulation of T3 availability in susceptibility to osteoarthritis

Waung J A , Sandison A , Bassett J H D , Williams G R

Local regulation of T3 action in bone and cartilage is a novel mechanism underlying the pathogenesis of osteoarthritis (OA). Accelerated chondrocyte differentiation is a hallmark of OA and T3 regulates this process. The type 1 and 2 deiodinases (D1, D2) convert the pro-hormone T4 to the active hormone T3 whilst D3 inactivates both T3 and T4. D1 contributes to circulating T3 levels and local T3</s...

ea0025oc4.3 | Bone and diabetes | SFEBES2011

Rapid bone turnover responses to increased hypothalamic–pituitary–thyroid-axis activity are mediated by thyroid hormones

Gogakos Apostolos , Murphy Elaine , Bassett Duncan , Williams Graham

Increased hypothalamic–pituitary–thyroid (HPT) axis activity results in high bone turnover. T3 stimulates osteoblast and osteoclast activities, whereas TSH is proposed to inhibit bone turnover directly. Resolving the relative importance of T3 and TSH is complicated by their physiological inverse relationship. We studied 10 controls and 4 patients with resistance to thyroid hormone (RTH), in which mutation of thyroid hormone receptor beta (THR...

ea0031p10 | Bone | SFEBES2013

High throughput detection of early joint pathology in mouse models of osteoarthritis

Draghici A E , Waung J A , Bassett J H D , Williams G R

Articular cartilage maintenance and repair is regulated by numerous endocrine and paracrine factors. Investigation of molecular mechanisms underlying osteoarthritis (OA) is limited by inability to identify early stage disease and individuals at risk of progression. Susceptibility to OA is genetically determined and the availability of mice from the International Knockout Mouse Consortium with deletions of every known gene provides a unique opportunity to investigate its pathop...