Endocrine Abstracts

The glucocorticoid receptor antagonist, RU486, binds to the glucocorticoid receptor (GR) with high affinity, and allows both nuclear localisation and also DNA binding. However, the DNA bound GR does not activate target gene transcription. This suggests that the ligand-binding domain of the GR is required to interpret agonist and antagonist ligands, and transmit those signals to the basal transcriptional machinery. Adaptor proteins play an important role in transducing the effe...

Glucocorticoids (Gc) are highly potent anti-inflammatory agents. They act through the glucocorticoid receptor (GR), a protein capable of multiple protein interactions. The pro-inflammatory cytokines, TNF-a and IL-1 signal, in part, through activation of NF-kB. Nf-kB transactivation is inhibited by activated GR. It has been suggested that the GR, and the p65 (RelA) component of NF-kB form a direct contact independent of Gc ligand, and that Gc binding results in inhibition of p6...

Objective: To assess age- and growth-dependent gene expression in children and correlate this with biological pathways.Methods: We conducted a gene expression meta-analysis on datasets from normal children curated from the NCBI Gene Expression Omnibus (GEO). Four datasets were combined to form a group of 87 individuals ranging from 0.2 to 29.3 years of age (average 7.7±6.9yr). Analysis of gene expression data was performed using hierarchical cluster...

Neuroendocrine tumours are slow growing and could be mistaken for other more malignant tumours with poorer prognosis. Their secretory profile may alter with time. The importance of awareness of these tumours and their clinical behaviour is illustrated by the case of a 78-year-old woman who presented with recurrent fasting hypoglycaemia.The patient had been diagnosed with metastatic pancreatic adenocarcinoma a year previously on the basis of radiographic ...

Aim: To investigate glucocorticoid (Gc) regulation of MIFBackground: MIF is a potent proinflammatory cytokine involved in inflammatory arthritis. Previous work suggested that MIF was induced by low concentrations of Gc, and may counteract their anti-inflammatory effect. The relationship between MIF and Gc has not been investigated in human cells.Methods: The human cell lines CEMC7A (T-lymphoblast) and A549 (lung epithelial) were us...

Background: Community based surveys have revealed that approximately 20% of patients taking thyroxine have low serum TSH concentrations. Likewise, a high proportion of patients (27%) have been found to have high TSH concentrations. Suboptimal thyroxine treatment, in particular overtreatment, is associated with significant potential health risks including atrial fibrillation and osteoporosis. In Sheffield, thyroxine treated patients are routinely enrolled on a computerised thyr...

Glucocorticoid receptor (GR) splicing may influence glucocorticoid sensitivity. We aimed to identify GR isoforms in the lung by using immunohistochemistry, immunoblotting, co-immunoprecipitation western and RT-PCR approaches.The distribution of GR protein in rat lung was different when we used an N terminal antibody (M20) compared to a C terminal antibody (GRalpha). M20 detected diffuse expression in all cell types and higher expression in the epithelium. In contrast GRalp...

Background: Neanderthals split from an ancestral human population ~500,000 years ago and lived in Eurasia until 40,000 years ago. Early modern humans emerged in Africa ~350,000 years ago migrating into Eurasia 50,000 years ago. Interbreeding occurred between early modern humans and Neanderthals leading to the introduction of Neanderthal DNA into the early human population, a process termed introgression. In modern Eurasian populations around 2-4% of DNA is of Neanderthal origi...

Background: Evidence suggests sex-specific differences in the development and progression of diabetic nephropathy (DN). Men and women have been shown to respond differently to certain therapies and epidemiological data suggest underuse of statins and renin-angiotensin system (RAS) blocking agents in women. We evaluated our local practice to identify differences in clinical characteristics and prescribing between men and women with DN.Methods: Clinical da...

Background: Recombinant human growth hormone (r-hGH) is the primary therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). There is a high cost associated with treatment and existing methods to predict response (and hence alter management) can only account for 40–60% of the variance.Methods: GHD (n=71) and TS patients (n=43) were recruited as part of a study (PREDICT) on the lo...