Searchable abstracts of presentations at key conferences in endocrinology

ea0010s21 | Evolving aspects in the HPA axis | SFE2005

Clinical and genetic aspects of glucocorticoid sensitivity

Ray D

Glucocorticoid hormones (Gc) are essential for human life, and synthetic glucocorticoids are widely used to treat inflammatory disease. Glucocorticoid action is mediated by the glucocorticoid receptor (GR).Strong linkage disequilibrium exists across the GR gene (r2=0.9) with, in our study, only 4 haplotypes (from a possible 1024) accounting for 95% of all those observed in UK Caucasian healthy individuals. We identified a 3-marker haplotype, across intro...

ea0009s29 | Symposium 7: The hypothalamic–pituitary–adrenal axis and inflammation | BES2005

Structure/function of the glucocorticoid receptor and its ligands

Ray D , #

Glucocorticoids powerfully inhibit inflammation by repressing NFkB function. We sought how ligand recognition by the glucocorticoid receptor (GR) regulates this effect. In vivo some glucocorticoid ligands (eg RU486) have negligible anti-inflammatory activity, in contrast to the agonist dexamethasone, despite promoting nuclear translocation of the GR, and binding to DNA. In-vitro studies have not identified a role for ligand binding in allowing interaction between the GR and NF...

ea0010p88 | Steroids to include Cushing's | SFE2005

Non-genomic effects of the glucocorticoid receptor - the effect of glucocorticoids on activation of c-src and PKB/Akt

Kayahara M , Berry A , Ray D

Glucocorticoids (Gc) are potent anti-inflammatory agents, but their clinical use is limited by their significant side effects. The effects of glucocorticoids are mediated by the cytosolic glucocorticoid receptor (GR), which regulates transcription by transactivation or transrepression. Independent of these genomic effects of the GR are other, very rapid non-genomic effects.The glucocorticoid receptor forms a complex with hsp90, FKBP51, FKBP52 and cyp40 i...

ea0003oc40 | Hormone Action | BES2002

RU486, the glucocorticoid receptor (GR) antagonist, recruits NCoR, but not SRC-1: Explaining type II antagonism

Stevens A , Garside H , Ray D

The glucocorticoid receptor antagonist, RU486, binds to the glucocorticoid receptor (GR) with high affinity, and allows both nuclear localisation and also DNA binding. However, the DNA bound GR does not activate target gene transcription. This suggests that the ligand-binding domain of the GR is required to interpret agonist and antagonist ligands, and transmit those signals to the basal transcriptional machinery. Adaptor proteins play an important role in transducing the effe...

ea0003p237 | Signalling | BES2002

Analysis of GR/NFkB interactions in living cells

Garside H , Stevens A , Ray D

Glucocorticoids (Gc) are highly potent anti-inflammatory agents. They act through the glucocorticoid receptor (GR), a protein capable of multiple protein interactions. The pro-inflammatory cytokines, TNF-a and IL-1 signal, in part, through activation of NF-kB. Nf-kB transactivation is inhibited by activated GR. It has been suggested that the GR, and the p65 (RelA) component of NF-kB form a direct contact independent of Gc ligand, and that Gc binding results in inhibition of p6...

ea0007p20 | Cytokines and growth factors | BES2004

Glucocorticoids suppress macrophage migration inhibitory factor (MIF) expression in a cell-type specific manner

Alourfi Z , Donn R , Stevens A , Ray D

Aim: To investigate glucocorticoid (Gc) regulation of MIFBackground: MIF is a potent proinflammatory cytokine involved in inflammatory arthritis. Previous work suggested that MIF was induced by low concentrations of Gc, and may counteract their anti-inflammatory effect. The relationship between MIF and Gc has not been investigated in human cells.Methods: The human cell lines CEMC7A (T-lymphoblast) and A549 (lung epithelial) were us...

ea0005oc16 | Cardiovascular Endocrinology | BES2003

Identification of novel glucocorticoid receptor isoforms in rat and human lung

Pan X , Stevens A , Davis J , Ray D

Glucocorticoid receptor (GR) splicing may influence glucocorticoid sensitivity. We aimed to identify GR isoforms in the lung by using immunohistochemistry, immunoblotting, co-immunoprecipitation western and RT-PCR approaches.The distribution of GR protein in rat lung was different when we used an N terminal antibody (M20) compared to a C terminal antibody (GRalpha). M20 detected diffuse expression in all cell types and higher expression in the epithelium. In contrast GRalp...

ea0019p310 | Steroids | SFEBES2009

Simultaneous measurement of cortisol and cortisone in saliva by LC-MS/MS: application in basal and stimulated conditions

Perogamvros I , Owen L , Ray D , Trainer P , Keevil B

Salivary cortisol is an increasingly popular tool in endocrine, psychological and sports studies. Immunoassays used for its measurement are limited by cross-reactivity from related steroids, mainly cortisone, which is abundant in saliva.A method was developed for the simultaneous measurement of cortisol and cortisone (SalF and SalE respectively) in saliva using LC-MS/MS. 40 μl of extract was injected onto a C8 4×2 mm guard cartridge attached to...

ea0009oc29 | Oral Communication 4: Steroids | BES2005

Characterisation of a novel protein interacting with the glucocorticoid receptor

Rice L , Waters C , Garside H , White A , Ray D

Glucocorticoids (Gcs) exert their pleiotropic effects through activation of the ubiquitously expressed glucocorticoid receptor (GR). The mechanism of transcriptional activation by the GR involves interaction with co-modulator proteins. Glucocorticoid sensitivity is mediated by the expression level of these co-modulator proteins and GR concentration. Therefore, the aim of this study was to identify additional GR interacting proteins that may influence glucocorticoid sensitivity...