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...

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...

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...

ea0031oc1.1 | Young Endocrinologists prize session | SFEBES2013

TNFα directly regulates in vivo corticosteroid metabolism in inflammatory arthritis

Nanus Dominika E , Filer Andrew , Fisher Benjamin A , Taylor Peter C , Stewart Paul , Buckley Christopher D , McInnes Iain , Cooper Mark S , Raza Karim

Within the synovium of patients with rheumatoid arthritis (RA), synovial fibroblasts generate active corticosteroids through expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). In vitro, this enzyme is strongly up-regulated by pro-inflammatory cytokines such as tumour necrosis factor α (TNFα) and IL1β. In this study, we determined the relationship between inflammation and global 11β-HSD1 activity in vivo, in a clini...

ea0094p66 | Metabolism, Obesity and Diabetes | SFEBES2023

Developing flare-responsive intra-articular steroid injections

Crastin Ana , S. Martin Claire , Sagmeister Michael , V. Adcock Holly , R. Adams Holly , Raza Karim , Filer Andrew , J. A. Moakes Richard , M. Grover Liam , S. Hardy Rowan

Intra-articular (IA) glucocorticoids (GCs) injections are effective in controlling joint inflammation but limited by short duration of action and off-target side effects. Gellan sheared hydrogels (SHs) area drug delivery vehicle, with unique thinning properties and enhanced release kinetics. We hypothesise that a combination of SHs and pre-receptor metabolism activated GCs provide slow-release drug delivery to target inflammation and minimise side-effects. We the release kinet...

ea0077p42 | Metabolism, Obesity and Diabetes | SFEBES2021

Chronic inflammation regulates androgen metabolism and exposure in Macrophages

Martin Claire S , Kalirai Matthew Singh , Crastin Ana , Turner Jason D , Schiffer Lina , Gilligan Lorna C , Taylor Angela E , Scheel-Toellner Dagmar , Raza Karim , Filer Andrew , Jones Simon W , Arlt Wiebke , Hewison Martin , Hardy Rowan S

Active androgens exert immunomodulatory actions at sites of inflammation and lower levels are implicated in the increased incidence of rheumatoid arthritis (RA) in females. However, inflammatory regulation of intracrine androgen metabolism within cell populations at sites of inflammation remain poorly defined. In this study we characterised immune and stromal cell androgen metabolism in RA patients and assessed their functional significance. Using the online Accelerating Medic...