Endocrine Abstracts

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 ...

Expansion of the orbital contents, by adipogenesis and hyaluronan (HA) overproduction, causes Graves orbitopathy (GO). Orbital HA is generated predominantly by hyaluronan synthase 2 (HAS2) whose transcription is positively regulated by pAkt in cell lines. GO is most frequently associated with Graves’ disease (GD) in which thyroid stimulating antibodies bind the TSH receptor (TSHR) increasing cAMP. Previous studies highlight a role for TSAB and ‘neutral’ TSHR ant...

Obesity (excess adipose tissue generated by hypertrophy and hyperplasia) predisposes to poor health. Adipogenesis (hyperplasia) involves the differentiation of adherent preadipocytes into non-adherent adipocytes and is accompanied by alterations to the extracellular matrix of which hyaluronan (HA) is a component. Used in vitro to promote lineage specific differentiation, little is known of HA’s role in adipogenesis. We hypothesise that HA modifications must occur d...

Objectives: Pregnancy and early infancy are periods when increased demand for thyroid hormone can result in subclinical hypothyroidism (SH). SH is frequently a prodrome to autoimmunity, but may be a compensation mechanism for an underlying genetic defect. The W546X mutation of the thyrotropin receptor (TSHR) is present at a frequency of 1 in 180 in a Caucasian population. We aimed to investigate whether W546X was the cause of SH presenting in pregnancy and early infancy.<p...

Introduction: The effects of mild subclinical hypothyroidism (SH; TSH <10 mU/l) on metabolic outcomes are unclear. This may relate to differences in aetiology, including thyroid autoimmunity or genetic factors such as TSH-receptor mutations (TSHR-M) and FOXE1 polyalanine tract length (FOXE1–PTL) polymorphisms, which are associated with altered thyroid function. We hypothesised that the metabolic manifestations of SH may depend upon its aetiology.<p class="abstext"...

Background: Alemtuzumab (ALTZ) is a humanised monoclonal anti-CD52 antibody used as effective treatment for relapsing/remitting multiple sclerosis (MS), causing panlymphopenia with subsequent lymphocyte repopulation. Unfortunately, around 40% of patients develop secondary humoral autoimmunity, mainly affecting the thyroid gland. Anti-thyrotropin-receptor (TSHR) autoantibodies (TRAb) can stimulate (TSAb), block (TBAb) or not affect (‘neutral’) TSHR function, with TSAb...

Background: Alemtuzumab (ALTZ) is a humanised monoclonal anti-CD52 antibody used as effective treatment for relapsing/remitting multiple sclerosis (MS), causing panlymphopenia with subsequent lymphocyte repopulation. Unfortunately, around 40% of patients develop secondary humoral autoimmunity, mainly affecting the thyroid gland. Anti-thyrotropin-receptor (TSHR) autoantibodies (TRAb) can stimulate (TSAb), block (TBAb) or not affect (‘neutral’) TSHR function, with TSAb...

Background: Changes of the gut microbiota may impact on the mechanisms of immune tolerance in Graves’ disease (GD) and Graves’ orbitopathy (GO). Probiotics, which contain live micro-organisms, can modify the composition of the gut microbiota.Aims: We tested in a double-blind randomized placebo controlled trial whether the administration of a well-characterized, commercially available, probiotic would 1) modify the microbiota composition in GD/G...