Endocrine Abstracts

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 ...

The liver produces and secretes sex hormone–binding globulin (SHBG), which transports sex steroids and regulates their access to tissues. Body mass index is a major determinant SHBG concentration in the blood of men and women. Low plasma SHBG levels are associated with obesity and predict the development of type 2 diabetes and cardiovascular disease. The reason why obese individuals have low circulating SHBG has been attributed to hyperinsulinemia, but no mechanistic evi...

The T cell immune system exists in a state of balance, poised to react to invading pathogens but at the same time constantly being restrained from attacking our own tissues. Several strategies are employed in order to minimise our own self-reactivity. First amongst these processes is the deletion of T cells in the thymus, however this process is incomplete and self-reactive T cells still populate our immune systems. A second layer of control is exerted by regulatory T cells (T...

Surgical parathyroidectomy remains the most cost effective treatment for primary hyperparathyroidism but where surgery is inappropriate because of significant co-morbidity there is a place for medical therapy. Calcimimetics are type II agonists (requiring calcium for activity) of the calcium sensing receptor (CaSR). The first compound of this class is cinacalcet which reduces PTH by about 50% at 4 h with recovery to within 20% of baseline over the next 8 h. Despite these fluct...

Sirtuins are NAD+-dependent deacetylases that are implicated in mediating health benefits of calorie restriction and possibly exercise. We will report on novel roles of SIRT1-3 in diseases of aging and recent progress in using small molecules to activate SIRT1. Small molecule activators of SIRT1 (STACs), such as resveratrol and SRT1720, improve multiple health parameters in mice including protection from type II diabetes and hepatic steatosis. We developed an system...

A significant portion of intercellular communication depends on protein secretion and interpretation of extracellular signals by transmembrane receptors. Proteins of both classes fold into their functional state in the lumen of the endoplasmic reticulum (ER), a process that is assisted by a dedicated machinery of ER-associated chaperones, enzymes and other components. The magnitude of this apparatus is matched to the load of unfolded proteins confronting the ER by a cell auton...

We are all prisoners of our faulted personalities, but only primary psychopaths use theirs systematically to target or imprison others. They lack the capacity to empathise, something normal people develop from early childhood. Considering people as objects, psychopaths survive by preying on what seems an incomprehensible weakness of normally empathic people. The condition of primary psychopathy is linked to lifelong dystunction of the amygdala, at the brain’s emotional co...

Testosterone is a well established, safe, effective and affordable hormone for use in androgen replacement therapy (ART) for androgen deficiency (AD) due to pathology of the hypothalamo-pituitary testicular axis. Newer testosterone products provide short-acting (transdermal) or long-acting (depot injectable) delivery with enhanced convenience to improve long-term compliance during life-long ART. Yet there is a striking disparity between major under-diagnosis of authentic AD (e...

Providing access to cutting edge technology and expertise in data analysis, the Genomic Services group at the WTCHG are empowering users to drive the pace of research into the underlying mechanisms of disease.The decade since the publication of the first full human genome has seen the development of sequencing technologies, fuelled by competitive pressure and the challenge of the $1000 genome. The latest High Throughput Sequencing platforms from LifeTech...

I live in Umbria and have recently become concerned for the young couple, Amanda Knox and Raffaele Sollecito, convicted of the horrific murder in Perugia on November 1st 2007 of English student Meredith Kercher, They were supposedly acting with an Ivorian, Rudy Guede, who was tried and convicted separately.I am still haunted by a wrongful conviction half a lifetime ago, which involved the murder of 11-year old Lesley Susan Molseed. Just before Christmas ...