Endocrine Abstracts

MC2R is the smallest member of the GPCR superfamily and belongs to the melanocortin subfamily of receptors. The pituitary hormone ACTH acts through MC2R to induce the intracellular production cAMP and the stimulation of steroidogenesis. We have previously shown that MC2R interacts with a single-transmembrane domain protein called MRAP (melanocortin-2 receptor accessory protein) and is required for the functional expression of MC2R. Both MC2R and MRAP are mutated in the rare re...

CD38 is an enzyme which catalyses the production of the second messengers cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate which mobilize calcium from ryanodine-sensitive intracellular calcium stores. Intracellular calcium is well known to be important for mobilisation of secretory granules to the plasma membrane in preparation for exocytosis and CD38 signalling has recently been demonstrated to increase posterior pituitary oxytocin release (Jin et al.</i...

Obesity, particularly abdominal (visceral) obesity, is a major risk factor for development of the metabolic syndrome. Human and animal studies have shown elevated intra-adipose glucocorticoid-action in obesity and suggest that increased glucocorticoid receptor (GR) density may be an important determinant of visceral adiposity. We have tested this hypothesis in transgenic (Tg) mice in which adipose GR levels have been increased or decreased, by expression of “sense” o...

Glucocorticoid (GC) excess is characterized by central obesity, insulin resistance and in some cases, type 2 diabetes mellitus. Whilst it is accepted that GCs cause insulin resistance, both insulin and GCs act synergistically to promote adipocyte differentiation. We have previously shown that acute treatment (24 h) with GCs enhances insulin signalling in human adipocytes. We hypothesise that the generation of cortisol from inactive cortisone by 11β-hydroxysteroid dehydrog...

We have created transgenic mice in which Cyp11b1, the gene encoding 11β-hydroxylase, has been knocked out. Since mice do not secrete adrenal androgens, this knockout line allows a more detailed investigation of phenotypes associated with congenital adrenal hyperplasia (CAH) without the overwhelming virilisation that characterises patients with CAH. Starting with a BAC containing the mouse Cyp11b1/b2 locus and including flanking up- and downstream sequences, a const...

The eye is an organ vulnerable to a variety of external and internal stimuli that can abolish its vital function to allow accurate vision of images for survival. Inflammation is the key mediator of immune protection but its consequence leads to the disruption of the visual axis integrity. Due to this precise reason, through adaptation and evolution, the eye has developed mechanisms of immune tolerance and privilege. Glucocorticoids have potent immunosuppressive and anti-inflam...

In addition to their documented impact on the cardiovascular system, polyunsaturated fatty acids (PUFAs) have also been shown to modulate steroidogenesis. However, the mechanistic nature of PUFA action on steroid synthesis remains unknown. PUFAs are recognised modulators of cholesterol trafficking. Liver X receptor (LXR) is a known cholesterol sensor that regulates a range of genes involved in cholesterol metabolism including Steroidogenic acute regulatory protein (StAR) which...

Glucocorticoids (Gcs) act via the intracellular glucocorticoid receptor (GR) to regulate cellular homeostasis. GR is a ligand-activated transcription factor which mediates effects within the nucleus or cytoplasm to regulate genomic or non-genomic events. Localisation of the GR to a specific cellular compartment is therefore an important determinant of the cellular response to Gcs.Live cell imaging of GR trafficking in cells transfected with fluorophore-t...