Searchable abstracts of presentations at key conferences in endocrinology

ea0025yep1.1 | Young endocrinologists’ prize lectures | SFEBES2011

New insights into glucocorticoid receptor function

Matthews Laura

The current model of glucocorticoid receptor (GR) action is well established, whereby GR remains inactive in the cytoplasm until bound by ligand, then rapidly translocates to the nucleus to regulate target genes. However, our recent observations challenge the simplicity of this model and suggest a greater range of GR action.We have identified a novel pathway in which the GR is recruited to the plasma membrane through binding to the lipid raft marker cave...

ea0028p323 | Steroids | SFEBES2012

Mitogen mediated Gc resistance, development of model using serum shock

Yang Nan , Trebble Peter , Matthews Laura , Ray David

Glucocorticoids (Gc) are the most potent anti-inflammatory agents known. A major factor limiting their clinical use is the wide variation in responsiveness to treatment between individuals and over time. Generating a reversible model of Gc resistance in vitro that will mimic the cellular microenvironment in vivo is critical in (i) defining biomarkers that predict patient steroid responsiveness; (ii) provide a model to screen new GR modulators capable of potentiating GR ...

ea0025oc2.6 | Steroids | SFEBES2011

Novel non-steroidal glucocorticoids that dissociate rapid signalling effects from gene transcription

Trebble Peter , Simpson Karen , Matthews Laura , Farrow Stuart , Ray David

Glucocorticoids (GCs) are used extensively in the treatment of inflammatory disease. Unfortunately, as GC act on virtually every organ system they also carry a broad range of serious side-effects which limits their clinical use.The structure of the bound GC strongly impacts the final conformation of the glucocorticoid receptor (GR) and thereby dictates downstream events. Designing drugs with different GR binding properties therefore offers a plausible ro...

ea0019p335 | Steroids | SFEBES2009

Epigenetic silencing of the GR and defining the pro-apoptotic actions of GR expression in human cancer cell lines

Kay Paul , Matthews Laura , Sommer Paula , White Anne , Ray David

Although glucocorticoids (Gc) are used to treat a range of pathologies, an individuals response to therapy varies considerably. There is a distinct correlation between certain cell types and steroid sensitivity. Aberrant glucocorticoid receptor (GR) function is well-characterised in lymphoid malignant cells but not small cell lung cancer (SCLC) (DMS79) or osteosarcoma (U2OS) cell lines, which are both Gc resistant.Previously we have shown reduced GR cont...

ea0013oc4 | Steroid synthesis and action | SFEBES2007

Modulation of membrane initiated glucocorticoid signalling by caveolin-1

Matthews Laura , Berry Andrew , Ohanian Jaqui , Ohanian Vasken , Ray David

Many glucocorticoid (Gc) actions are of rapid onset, and therefore require acute regulation of intracellular signalling cascades. We have previously identified rapid Gc-dependent activation of the caveolae specific integral membrane protein caveolin, and the cytosolic kinase PKB in the lung epithelial cells, A549.Immunofluorescence studies demonstrate the appearance of activated glucocorticoid receptor (P-ser211-GR) localised to focal points around the c...

ea0038oc3.2 | Steroids and adrenal | SFEBES2015

Glucocorticoids stabilise the microtubule network to inhibit cell migration

Kershaw Stephen , Morgan David , Poolman Toryn , Brass Andy , Matthews Laura , Ray David

Glucocorticoids (GCs) are steroid hormones used to treat inflammatory diseases such as rheumatoid arthritis, but their clinical efficacy is hampered by development of side effects such as impaired wound healing. GCs bind the glucocorticoid receptor (GR) to mediate cellular effects. The inactive GR is held in multi-protein complex in the cytoplasm and upon ligand binding undergoes a conformational change, interacts with cytoplasmic enzymes to mediate non-genomic effects (within...

ea0025p295 | Steroids | SFEBES2011

Systems biology reveals a novel mechanism regulating glucocorticoid action

Morgan David , Han Namshik , Matthews Laura , Norman Michael , Brass Andy , Ray David

Glucocorticoids act through the glucocorticoid receptor (GR) to regulate cell function. GR gamma (GRγ) is a constitutive exon3/4 splice variant, contributing 4–8% of the total GR transcripts and is highly conserved through mammalian evolution, but its biological function remains unknown. Using microarray analysis we identified the transcriptome response for GRγ in stable HEK-Flp cells. This revealed that although GRγ effectively modulated gene expression in...

ea0015oc32 | Pituitary, disease | SFEBES2008

Coupling of GR cellular distribution and function to the cell cycle

Matthews Laura , Spiller David , Rivers Caroline , Norman Michael , White Michael , Ray David

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...

ea0015p159 | Diabetes, metabolism and cardiovascular | SFEBES2008

Rosiglitazone activates the glucocorticoid receptor

Matthews Laura , Berry Andrew , Tersigni Mariaroberta , D'Acquisto Fulvio , Ianaro Angela , Ray David

Synthetic peroxisome proliferator-activated receptor gamma (PPARγ) ligands are used clinically to improve insulin sensitivity. Although designed as specific ligands for PPARγ, there is evidence for some ‘off target’ effects being mediated by a non-classical, non-PPARγ mechanism. Recent evidence further suggests that some of these effects may be glucocorticoid receptor (GR)-dependent.To analyse activation of GR following exposure ...

ea0050oc4.2 | Adrenal and Steroids | SFEBES2017

Glucocorticoids rapidly inhibit cell migration through a novel, non-transcriptional pathway involving HDAC6

Kershaw Stephen , Morgan David , Boyd James , Spiller David , Iqbal Mudassar , Zindy Egor , Brass Andy , Matthews Laura , Ray David

Glucocorticoids (Gc) act through the glucocorticoid receptor (GR) to regulate immunity, energy metabolism, and tissue repair. The inactive GR is held in the cytoplasm in a multi-protein complex, which upon ligand binding undergoes a conformational change. Activated GR translocates to the nucleus to regulate gene expression (over hours), but some effects occur more rapidly. Gc inhibit cell migration through an uncertain mechanism. We now show a very rapid effect, and surprising...