Endocrine Abstracts

The anorexigenic hormone leptin seems to be the principal adiposity indicator and signal of the state of nutrition, as its plasma levels are highly correlated to adipocyte number and fat content. The elucidation of the causes of monogenic forms of obesity has benefited from the positional cloning of a series of mouse obesity genes, including those that encode leptin, the leptin receptor (LEPR). Targeted genetic manipulation has also established the vital regulatory role of mol...

Parathyroid hormone (PTH) exerts important metabolic effects on the kidney and is responsible for regulating phosphate transport by proximal tubules and calcium absorption by distal tubules. These effects are mediated by the type 1 PTH receptor (PTH1R), which is prominently expressed in both nephron segments. However, the signaling pathways employed by proximal and distal PTH1Rs differ markedly. Recent work reveals the apparent basis by which PTH receptors signal through cAMP ...

Glucocorticoids are by far the most effective anti-inflammatory therapy for asthma (and many other inflammatory diseases). Glucocorticoids bind to glucocorticoid receptors in the cytoplasm and translocate to the nucleus, where they interact as dimers with glucocorticoid response elements in the promoter region of steroid-sensitive genes to switch on transcription of anti-inflammatory genes, (such as MKP-1). This involves binding of GR to coactivator proteins and acetylation of...

Adrenal insufficiency may occur because of primary failure of the adrenal cortex but can also arise through a secondary failure of ACTH drive to the adrenal. 'Endogenous' suppression of the adrenal cortex may occur in patients with structural abnormalities affecting the hypothalamus/pituitary and in other patients with deficiency of pituitary ACTH secretion and action including those recovering from successful treatment of Cushing's syndromes. 'Exogenous' suppression is found ...

Osteoporosis has increasingly been recognised as a major healthcare problem. In the past diagnosis was predicated upon the results of bone density measurements with the WHO threshold of a T score of -2.5 being taken as diagnostic. This approach is being called into question as the importance of factors other than bone density upon the risk of fracture have emerged. It is likely that treatment for osteoporosis will soon be decided upon the basis of estimated fracture risk rathe...

A series of reports have highlighted the lack of career structure and incentive for both clinical and non-clinical scientists wishing to pursue an academic career. For non-clinical personnel this is particularly critical as Endocrinology risks losing some of its identity to newer disciplines such as cell biology and signalling. The current inability to train clinical academics and basic scientists in Endocrinology represents a major threat to the discipline as a whole and must...

Embryos heal wounds very rapidly and efficiently and without leaving a scar. Studying how they do this can tell us much about the natural morphogenetic movements of embryogenesis as well as suggesting ways in which we might make adult tissues repair more efficiently. Using live confocal imaging of transgenic Drosophila embryos expressing gfp-actin in epithelial tissues we have revealed the key actin machineries that drive the paradigm morphogenetic process of dorsal closure wh...

Body Mass Index is an inheritable trait, and the intra familial relative risk to develop obesity is around 5. Genome Scans in Human provided a number obesity loci. The most replicated regions of linkage map on chromosome 2p, 7q and 10p but other potentially strong loci have been found on chromosome 4, 5, 6, 11, 12, 20..The availability of extensive data bases of SNPs has made possible the positional cloning of obesity. We have recently investigated chrom...

In recent years there has been considerable progress in identifying how insulin signals to the cell's interior. The interaction of insulin with its receptor triggers the formation of phosphatidyl inositol (3, 4, 5) trisphosphate (PIP3) at the plasma membrane which then activates several signal transduction pathways. Perhaps the most important of these is the protein kinase cascade in which 3-phosphoinositide-dependent protein kinase-1 (PDK1) activates protein kinase B (PKB, al...

Primary hyperparathyroidism is one of the most common endocrine conditions affecting upto 2% of postmenopausal women. Diagnosis is primarily biochemical and is usually secure when a persistently elevated plasma calcium is found together with parathyroid hormone (PTH) concentrations above the middle of the normal range. The only other circumstance which can produce a similar picture is familial benign (hypocalciuric) hypercalcaemia (FBH) which is an inherited disorder oc calciu...