Endocrine Abstracts

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...

Similar to thyroid hormones, the calcineurin/NFAT pathway regulates bone mass via its actions in osteoblasts and by indirect effects on osteoclast function. Calcineurin is a calcium- and calmodulin-activated phosphatase that dephosphorylates the transcription factor NFAT enabling its translocation to the nucleus. RCAN2 is an inhibitor of calcineurin that is stimulated by T3 in brain, heart and skeletal muscle although its expression in bone has not been studied. Thu...

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...

The prohormone T4 represents the majority of circulating thyroid hormones, whereas 80% of the active hormone T3 is derived from T4 by the actions of the type 1 and type 2 deiodinase enzymes (D1 and D2). Local generation of T3 by D2 regulates ligand supply to the nuclear T3-receptor in pituitary, brown adipose tissue and brain, and this enzyme is also expressed in bone. Hypothyroidism in children causes delayed bone age and growth retardation, whereas thyrotoxicosis in adults c...

T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter-8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compo...

T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter-8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compo...

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...