Endocrine Abstracts

The insulin-like growth factors (IGFs) are important regulators of cellular function, with effects on growth, survival and metabolism mediated primarily through the type 1 IGF receptor (IGFIR). Recent work suggested that localisation of IGFIR to a subset of lipid rafts, known as caveolae, may be important for IGF function. In this study we have investigated whether these membrane domains were involved in IGF-I-mediated cell survival by comparing signalling in caveolae-positive...

Variation in glucocorticoid (Gc) sensitivity underlies metabolic disease, and affects therapeutic response in inflammation. Using an in-vitro screening approach we identify two new mechanisms capable of regulating Gc sensitivity.The first involves interferon induced factor 16 (IFI16). IFI16 potentiated both transactivation, and Gc repression of NFκB. IFI16 did not affect glucocorticoid receptor (GR) expression, ligand dependent repression of GR expr...

Glucocorticoids (GCs) are the most potent anti-inflammatory agents known and are used extensively in the treatment of inflammatory disease, however an individuals response to therapy varies greatly. Resistance to GC is often attributed to mutations within the glucocorticoid receptor (GR) through which GC elicit their effects. Here, we present a kindred with GR haploinsufficiency yet no clinical phenotype. PCR and GR sequence profiling of genomic DNA isolated from patient blood...

Glucocorticoids (Gcs) act via the intracellular glucocorticoid receptor (GR) to regulate cellular homeostasis. GR is a ligand-activated transcription factor that mediates effects within the nucleus or cytoplasm to regulate genomic and 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 using fluorophore-tagged GR shows drama...

The actions of glucocorticoids (Gc) are mediated by the glucocorticoid receptor (GR). Several isoforms of the GR exist. Whilst GR alpha is the most abundant isoform, constitutive alternative splicing at the exon 3/exon 4 boundary results in an additional arginine within the DNA binding domain to produce the gamma isoform. Although GR gamma comprises 4–8% of total GR transcripts and is highly conserved through mammalian evolution, its biological function remains unknown.</...

Glucocorticoids (Gcs) act via the intracellular glucocorticoid receptor (GR) to regulate cellular homeostasis. Previous studies have demonstrated altered Gc sensitivity during mitosis. This reduced sensitivity can be explained only in part through the selective export of GR in mitotic cell populations. In this study ligand-independent, cell cycle-dependent effects on GR have been explored.Mitotic cells show a marked increase in ligand-independent ser211 ...

Glucocorticoids (Gc) act through the glucocorticoid receptor (GR) to regulate gene transcription, but also initiate a number of rapid non-genomic effects. The inactive GR is found complexed with hsp90 and immunophilins. Several other signalling molecules including c-src and raf-1 also associate with hsp90. Evidence suggests that Gc treatment results in the rapid activation and dissociation of GR and c-src from these complexes. We speculate that GR-mediated activation of one or...