Endocrine Abstracts

We all live in an oscillating environment driven by the Earth’s rotation. This imposes predictable patterns of light and dark, to which almost all of life responds. There is a survival advantage in anticipating such environmental change, which has led to evolution of the autonomous circadian clock.The circadian clock controls up to 40% of biochemical pathways, often acting to control a rate-limiting enzymatic step. Therefore, design and interpretati...

We all live in an oscillating environment driven by the Earth’s rotation. This imposes predictable patterns of light and dark, to which almost all of life responds. There is a survival advantage in anticipating such environmental change, which has led to evolution of the autonomous circadian clock.The circadian clock controls up to 40% of biochemical pathways, often acting to control a rate-limiting enzymatic step. Therefore, design and interpretati...

The glucocorticoid receptor (GR) is a nuclear receptor, a major drug target, and the end point of the hypothalamic-pituitary-adrenal axis. Glucocorticoids (GC) are essential for life, but in excess cause disordered energy metabolism, including increased weight gain, adiposity and hepatosteatosis; all programmes modulated by the circadian clock. Secretion of GC is regulated by the circadian clock, but could their actions be also? Here, using mouse as a model, we found that whil...

The glucocorticoid receptor (GR) is a ligand activated transcription factor, serving to regulate both energy metabolic and immune functions. The natural endogenous glucocorticoid in humans is cortisol, but a variety of synthetic molecules have been developed to treat inflammatory disease. These synthetic ligands offer new insights into how the GR works, and how it can be manipulated. Novel, non-steroidal GR agonists specifically alter the GR LBD structure at the HSP90 binding ...

Glucocorticoid hormones (Gc) are essential for human life, and synthetic glucocorticoids are widely used to treat inflammatory disease. Glucocorticoid action is mediated by the glucocorticoid receptor (GR).Strong linkage disequilibrium exists across the GR gene (r2=0.9) with, in our study, only 4 haplotypes (from a possible 1024) accounting for 95% of all those observed in UK Caucasian healthy individuals. We identified a 3-marker haplotype, across intro...

Glucocorticoids powerfully inhibit inflammation by repressing NFkB function. We sought how ligand recognition by the glucocorticoid receptor (GR) regulates this effect. In vivo some glucocorticoid ligands (eg RU486) have negligible anti-inflammatory activity, in contrast to the agonist dexamethasone, despite promoting nuclear translocation of the GR, and binding to DNA. In-vitro studies have not identified a role for ligand binding in allowing interaction between the GR and NF...

Introduction: Insulin Dugludec is an ultra- long acting basal insulin. The management of diabetes in children is challenging due to the need of regularly injecting insulin, risk of hypoglycaemia, variation in the activity of different insulins available. Dugludec has a long half-life (25 hrs), lower variability and lasts 42 hours. Currently there are no guidelines or NICE recommendations advising the use of insulin dugludec in children with diabetes. Studies are few but have s...

Professor David RayDavid Ray graduated in Medicine from University of Manchester in 1987. He trained in medicine and endocrinology in the North West, before doing a PhD with Anne White and Julian Davis, again in Manchester. Towards the end of his PhD he was offered a post with Shlomo Melmed at UCLA, and, attracted by the lab, and the adjacent coast, headed west. This research post stimulated an ...

Xanthoma Disseminatum: A rare cause of hypopituitarismS Ray and PE Belchetz; The General Infirmary at Leeds, Leeds, UK.Xanthoma disseminatum (XD) is a rare, benign, normo-lipaemic condition characterised by non- Langerhan's cell histiocytosis which usually effects male children or young adults. Patients develop nodular or infiltrating papules that are distributed along flexural areas and mucosal surfaces. Meningeal infiltration ca...

Small cell lung cancer (SCLC) is an aggressive neuro-endocrine tumour with an abysmal prognosis. These cancers are characteristically resistant to glucocorticoid (Gc) action, and display glucocorticoid receptor (GR) abnormalities. We therefore selected model cell lines displaying reduced GR expression and Gc insensitivity as tractable in vitro systems in which to discover the effects of restored GR expression. GR fused to the yellow fluorescent protein, eYFP, was over-e...