Endocrine Abstracts

Chronic inflammatory disease is often accompanied by angiogenesis and fibrosis. Glucocorticoids (GCs) exert anti-inflammatory and anti-angiogenic effects, in which macrophages are a major target. Local endogenous GC action is controlled by 11β-hydroxysteroid dehydrogenase (11β-HSD), with the type 1 isozyme, 11β-HSD1 converting inactive GCs into active forms. Mice deficient in 11β-HSD1 have a phenotype consistent with reduced glucocorticoid action, including...

Background: Recent studies have shown that adult human possess active brown adipose tissue (BAT), which might be important in affecting obesity and related metabolic risk. However, the supporting evidence in large population based studies is sparse.Methods: We studied 4011 (2688 males and 1323 females) tumor-free Chinese adults aged 18–89 for BAT activities, visceral/subcutaneous fat areas and metabolic parameters. In vivo 18F-fluorodeoxygluc...

The purpose of the present study was to elucidate expressions of ERβ1 and ERβ2 expression in papillary thyroid cancer (PTC). ER β splicing variants expressions were examined on formalin-fixed, paraffin-embedded thyroid tissues from 106 PTCs and 30 nodular thyroid goiters (NTGs) by immunehistochemical methods using Elivision plus two-step system. There was significant difference in the subcellular localization of ERβ1 expression (P<0.001), but not...

Clear evidence on the specific impact of fatty acid binding proteins (FABPs) on cell biology and lipid metabolism in complex systems had been lacking until FABP-deficient mice models were created. Surprisingly, no change in appearance, gross morphology or viability was observed in FABP1-deficient mice. However, metabolic parameters in mice upon exposure to high-fat/cholesterol diet differed between studies. Therefore, liver fatty acid-binding protein (also called FABP1) plays ...

Background: Cushing’s disease is associated with high morbidity and mortality, and there are currently no approved medical therapies. Twice-daily pasireotide sc showed efficacy in patients with mostly moderate-to-severe (UFC≥2×ULN) Cushing’s disease in a large, randomized, double-blind, 12-month trial. A monthly long-acting release (LAR) formulation of pasireotide has been developed to provide a smoother pharmacokinetic profile, potentially a better effica...

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...

Introduction: Pasireotide reduced UFC levels in 22 of 29 patients with Cushing’s disease after 15 days’ treatment (Boscaro et al. JCEM 2009). Of these 22 patients, 5 achieved normalized UFC (UFC-responders) and 17 had reduced but not normalized UFC (UFC-reducers). Results of an extension phase to this study are presented.Methods: Patients with de novo or persistent/recurrent Cushing’s disease received pasireotide 600 μg ...

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...

Strong gain-of-function mutations have not been identified in humans in the FSH receptor (FSHR), while such mutations are common among many other G-protein-coupled receptors. In order to predict consequences of such mutations on humans, D580 (D6.44) mutant forms of mouse (m) FSHR were expressed under the human anti-Müllerian hormone promoter in transgenic mice. Transgenic expression of mFshrD580H in granulosa cells led to abnormal ovarian structur...

The thyrotropin receptor (TSHR) is expressed in the thyroid and in precursors undergoing lineage-specific differentiation, e.g adipogenesis. The TSHR is activated by TSH, thyroid stimulating antibodies (TSAB) and gain-of-function mutations (TSHR*). To investigate the role of extra-thyroidal TSHR activation we compared the gene-expression profiles of non-modified human subcutaneous preadipocytes with the parallel TSHR* population. Twenty-seven genes were significantly upregulat...