Endocrine Abstracts

Introduction: There has been a substantial increase in our knowledge of the genetic architecture of thyroid function, with numerous variants associated with TSH and/or FT4 levels. However, our knowledge of the genetic variants associated with thyroid disease is more limited.Methods: Data was obtained from the Neale laboratory† which provided a case-control study to identify single nucleotide polymorphisms associated with a diagnosis of hypothyroidi...

Thyrotropin receptor (TSHR, signals via CREB) expression increases during adipogenesis, a process occurring in Graves’ orbits. CREB activation has been reported ‘necessary and sufficient’ to induce adipogenesis. However, we previously demonstrated that expression of constitutively active TSHR in orbital preadipocytes stimulated early but inhibited later differentiation stages, even when PPARγ agonist induced. Overproduction of proteoglycans is also a featur...

Background: CB1 antagonism has potential benefits in the metabolic syndrome, with effects mediated through central orexigenic mechanisms and peripheral action on adipose tissue. We have previously demonstrated the inhibitory effects of CB1 inactivation on preadipocyte proliferation and now extend these studies to in vitro adipogenesis.Aims: To compare the effects of CB1 agonism and antagonism on differentiation in both preadipocyte cell lines and ...

TSH receptor (TSHR) expression increases >100-fold during adipogenesis and signals via CREB. Since CREB activation has been reported to be ‘necessary and sufficient to induce adipogenesis’, we investigated whether TSHR activation, a feature of most thyroid dysfunction, has a role in adipocyte biology and evaluated the contribution of Gsα and Gβγ signalling.Retroviral vectors for WT or constitutively active mutant TSHR* or ...

Dehydroepiandrosterone (DHEA) is an adrenal sex steroid whose levels decline during normal aging. Epidemiological studies demonstrate inverse correlation between circulating DHEA-sulphate and body fat mass while DHEA administration in elderly subjects reduces visceral and subcutaneous fat accumulation. Although previous studies have shown that some effects may be mediated via DHEA-induced inhibition of white pre-adipocyte proliferation, mechanisms remain unknown. Furthermore, ...

Patients with non-functional FOXE1 (forkhead transcription factor) display congenital hypothyroidism, ‘spikey’ hair and other abnormalities. In the thyroid, FoxE1 controls migration of the developing gland and adult expression of thyroid specific genes. Our earlier studies demonstrated FOXE1 protein expression in keratinocytes of the epidermis and hair-follicle outer root sheath.We aimed to characterise the expression and functional activity of...

In addition to its central role in the control of thyrocyte growth and function, the TSHR is expressed during the differentiation of mesenchymal precursors. To explore further, we have developed an in vitro model in which TSHR activation is achieved by introducing constitutively active (M453T, L629F) TSHR, using retroviral vectors.We aimed to investigate the effect of TSHR activation on body composition, via the production of TNFα and express...

Adipogenesis is induced when intracellular cAMP increases and follows cell cycle arrest. During preadipocyte differentiation expression of the TSHR, which signals via cAMP and the inositol phosphate cascade, is upregulated. To investigate the role of TSHR activation in adipogenesis, we have developed an in vitro model in which constitutively active TSHR mutants (L629F, M453T) are introduced by retroviral vectors (RV).We aimed to compare the effect...

The TSHR is expressed during adipogenesis. We have employed in vitro models to investigate how TSHR activation affects this process. Gain-of-function TSHR mutants were introduced into preadipocytes using retroviral vectors. We have demonstrated that TSHR activation inhibits their proliferation and PPAR-gamma agonist (pioglitazone) induced adipogenesis. The aim of this study was to investigate the mechanisms operating.Non-modified primary human preadipocy...

Graves' disease (GD) is caused by thyroid stimulating antibodies (TSAb) which are thyrotropin (TSH) agonists. Thyroid peroxidase (TPO) antibodies, although markers of thyroid auto-immunity are not involved in the pathogenesis of GD. Despite this, TPO antibodies are frequently used to establish the etiology of thyrotoxicosis. It was our aim to compare TPO antibodies with TSAb in a cohort of thyrotoxic patients to determine whether TPO antibodies and TSAb could be regarded as eq...