Searchable abstracts of presentations at key conferences in endocrinology

ea0065oc5.4 | Adrenal and Cardiovascular | SFEBES2019

Pre-receptor metabolism and signalling of glucocorticoids between macrophages and fibroblasts

Martin Claire , Fenton Chloe , Filer Andrew , Hewison Martin , Clark Andy , Hardy Rowan

The glucocorticoid (GC) activating enzyme 11β-HSD1 is potently upregulated within macrophages and synovial fibroblasts of inflamed joints, where it increases therapeutic GC signalling and regulates their anti-inflammatory profiles. Whilst in vitro studies have demonstrated the importance of autocrine signalling in this context, the importance of paracrine signalling remains poorly defined. In this study, we examined the role of 11β-HSD1 in paracrine GC signalling bet...

ea0044p10 | Adrenal and Steroids | SFEBES2016

11β-Hydroxysteroid Dehydrogenase Type 1 within Muscle Protects Against the Adverse Effects of Local Inflammation and Muscle Wasting

Hardy Rowan , Hussain Zahrah , Filer Andrew , Buckley Christopher , Lavery Gareth , Cooper Mark , Raza Karim

Muscle wasting is a common feature of inflammatory myopathies. Glucocorticoids (GCs), whilst effective at suppressing inflammation and inflammatory muscle loss, also cause myopathy with prolonged administration. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bidirectional GC activating enzyme, potently up-regulated by inflammation within mesenchymal derived tissues. We assessed the regulation of this enzyme with inflammation in muscle and examined its functi...

ea0025p118 | Cytokines, growth factors, neuroendocrinology and behaviour | SFEBES2011

Impact of synovial fibroblasts on adipose tissue

Hussain Ahkeb , Hardy Rowan , Patel Pushpa , Ahassan Mohammad , Filer Andrew , Stewart Paul , Cooper Mark

Rheumatoid arthritis (RA) is associated with a loss of lean mass and a corresponding increase in fat mass. How fat accumulation in RA is linked to synovial inflammation is unknown. Wnts comprise a family of secreted glycoproteins that are crucial in regulating adipocyte proliferation, apoptosis and differentiation. Recently we demonstrated that endogenously generated glucocorticoids (GCs) alter the pattern of wnt secretion by synovial fibroblasts (SFs), favouring production of...

ea0009oc32 | Oral Communication 4: Steroids | BES2005

Differential induction of fibroblast 11beta-HSD1: a mechanism for tissue-specific regulation of inflammation

Hardy R , Cooper M , Filer A , Parsonage G , Buckley C , Stewart P , Hewison M

Acute inflammation plays an important role in the normal immune system by helping to coordinate host responses to danger signals such as infection. In most cases the inflammation is rapidly resolved but in chronic inflammatory diseases such as rheumatoid arthritis (RA) the inflammation persists leading to localized accumulation of potentially damaging immune cells. It remains unclear why inflammation persists in some tissues and not in others. Recent studies have shown that st...

ea0007p13 | Bone | BES2004

The role of local corticosteroid generation in inflammation-associated bone loss

Cooper M , Filer A , Moore J , Emery P , Buckley C , Hewison M , Stewart P

Generalised and periarticular osteoporosis are common features of inflammatory arthritides. These effects appear due to high levels of pro-inflammatory cytokines. 11beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) is an intracellular enzyme that generates active cortisol from inactive cortisone and is an important determinant of the effects of glucocorticoids on osteoblasts. In vitro, osteoblastic 11b-HSD1 expression is induced by pro-inflammatory cytokines. We thus ...

ea0005p215 | Steroids | BES2003

11Beta-hydroxysteroid dehydrogenase in human fibroblasts: Expression and regulation depends on tissue of origin

Moore J , Filer A , Buckley C , Stewart P , Hewison M , Cooper M

Fibroblasts are important regulators of local inflammatory responses. These responses are further regulated by tissue glucocorticoid levels. Other stromal lineage cells, adipocytes and osteoblasts, express 11beta-hydroxysteroid dehydrogenases (11b-HSDs) which interconvert inactive cortisone and active cortisol. These enzymes are important regulators of local glucocorticoid levels and their expression is regulated by proinflammatory cytokines. We therefore examined expression o...

ea0034p368 | Steroids | SFEBES2014

Glucocorticoid activation in muscle by 11β-hydroxysteroid dehydrogenase type 1: contributions to inflammatory muscle wasting

Hardy Rowan , Lavery Gareth , Pierson Mark , Doug Craig , Filer Andrew , Buckley Christopher , Lord Janet , Stewart Paul , Cooper Mark , Raza Karim

Muscle wasting remains a significant complication in patients with inflammatory disease where it contributes to disability, risk of falls and early mortality. Interestingly, muscle wasting in patients with glucocorticoid excess mirrors that observed in patients with inflammatory disease. We have previously reported that the glucocorticoid activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is potently up-regulated within mesenchymal derived cell popu...

ea0021oc3.7 | Young Endocrinologists prize session | SFEBES2009

Effects of glucocorticoids on Wnt gene expression in synovial fibroblasts: potential role in inflammatory bone loss

Hardy Rowan , Patel Pushpa , Ahasan Mohammad , Rabbitt Elizabeth , Filer Andrew , Raza Karim , Buckley Chris , Stewart Paul , Cooper Mark

Synovial fibroblasts (SFs) form a substantial component of inflamed rheumatoid synovium and generate endogenous glucocorticoids (GCs) during inflammation. Recently, production of DKK-1 (a Wnt signalling inhibitor that reduces bone formation) by SFs in response to TNFα has been proposed to be the master regulator of inflammatory osteoporosis. We have identified that in addition to TNFα, GCs potently induce DKK-1 secretion. This may provide a novel mechanism whereby lo...

ea0019oc6 | Young Endocrinologist prize session | SFEBES2009

Locally generated glucocorticoids, rather than pro-inflammatory cytokines, directly regulate synovial DKK-1 expression in inflammatory arthritis

Hardy R , Ahasan M , Patel P , Filer A , Rabbitt E , Raza K , Stewart P , Buckley C , Cooper M

We have previously proposed a central role for locally generated glucocorticoids in the periarticular and systemic osteoporosis seen in rheumatoid arthritis (RA). Synovial fibroblasts (SFs) express the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme and this expression increases dramatically with inflammation. Recently, production of DKK-1 (a Wnt signalling inhibitor known to inhibit bone formation) by SFs in response to inflammation has been proposed to ex...

ea0034p351 | Steroids | SFEBES2014

High 11β-HSD1 activity is associated with progression to rheumatoid arthritis in patients first presenting with inflammatory arthritis

Nanus Dominika , Filer Andrew D , Yeo Lorraine , Scheel-Toellner Dagmar , Hardy Rowan , Lavery Gareth L , Stewart Paul M , Buckley Christopher D , Cooper Mark S , Raza Karim

Variation in endogenous glucocorticoid (GC) activity during inflammation has been linked to susceptibility to developing rheumatoid arthritis (RA). It has been shown that in patients with RA inflamed synovial tissue can generate active GCs through the expression of the 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1), which converts cortisone to cortisol. We examined whether the total body activity of 11β-HSD1 or its expression within synovium was assoc...