Endocrine Abstracts

Objective: Therapeutic glucocorticoids (GCs) are commonly used in the treatment of chronic inflammatory disease. Unfortunately, their long-term administration is associated with deleterious systemic side effects including muscle atrophy. 11 beta-hydroxysteroid dehydrogenase type 1 (11βHSD1) activates glucocorticoids within muscle, is increased with inflammation, and has previously been shown to mediate GC induced muscle wasting. We examined the role of 11 beta-hydroxyster...

Glucocorticoids (GCs) have potent immunomodulatory and anti-inflammatory effects and are widely used in the treatment of inflammatory diseases. Unfortunately, their long term administration causes serious systemic metabolic side effects including osteoporosis, muscle wasting and insulin resistance. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is responsible for the local conversion of inactive GCs to their active counterparts. It has been shown that many of the...

Local and systemic bone loss is a common complication in patients with chronic inflammatory disease. Previously, we have identified that glucocorticoid (GC) activation by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is increased within tissues such as bone during systemic inflammation. However, whilst effective at suppressing inflammation, in excess, GCs drive osteoporosis. To determine the contribution of 11β-HSD1 activated glucocorticoids to inf...

Glucocorticoids (GCs) have potent immunomodulatory and anti-inflammatory effects and are widely used in the treatment of inflammatory diseases. Unfortunately, their long term administration causes serious systemic metabolic side effects including osteoporosis, muscle wasting and insulin resistance. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is responsible for the local conversion of inactive GCs to their active counterparts. It has been shown that many of the...

Local and systemic bone loss is a common complication in patients with chronic inflammatory disease. Previously, we have identified that glucocorticoid (GC) activation by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is increased within tissues such as bone during systemic inflammation. However, whilst effective at suppressing inflammation, in excess, GCs drive osteoporosis. To determine the contribution of 11β-HSD1 activated glucocorticoids to inf...

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...

Objective: Therapeutic glucocorticoids (GCs) are used to treat chronic inflammatory disease, due to their anti-inflammatory effects. Despite their efficacy, chronic exposure to GCs elicits undesirable side effects, including muscle atrophy. 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) activates GCs within muscle, is induced by inflammation, and has previously shown to drive GC-induced muscle wasting. We examined the role of 11β-HSD1 in mediating muscle wasting i...

Both therapeutic glucocorticoids (GCs) and chronic inflammation are powerful inducers of systemic bone loss, resulting in osteoporosis and increased morbidity. Whilst GCs suppress inflammation, it is unclear how these factors interact to determine net bone metabolism. We investigated the balance between osteo-protective and osteo-destructive properties of GCs in the TNF-tg model of chronic inflammatory disease. Wild-type (WT) and TNF-tg mice were treated with corticosterone (1...

In chronic inflammatory disease, an increased proportion of M1 polarised macrophages have been shown to contribute to inflammation and tissue damage through the production of pro-inflammatory cytokines such as TNFα. Previously, we have identified expression of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which converts inactive glucocorticoids (GCs) to their active counterparts, in M1 polarised macrophages in vivo. We hypothesised that 11β...