Endocrine Abstracts

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...

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...

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...

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...

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 ...

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...

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...