Endocrine Abstracts

Background: Acidosis activates the hypothalamic-pituitary-adrenal (HPA) axis and induces glucocorticoid-mediated atrophy of skeletal muscle. The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive cortisone to active cortisol and modulates glucocorticoid signalling locally within skeletal muscle. Here, we address a gap in knowledge how acidosis affects 11β-HSD1 activity in human skeletal muscle cells.Methods: Quadrice...

Background: Chronic kidney disease aggravates loss of skeletal muscles mass and function, which is an independent risk factor for hospitalisation, morbidity and mortality. Glucocorticoid signalling has been implicated as a critical factor in the pathogenesis of muscle atrophy in kidney disease. This study tests whether genetic deletion of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11bHSD1) protects against muscle atrophy in the adenine-die...

Introduction: Chronic kidney disease (CKD) is characterised by an ongoing reduction in kidney function and is associated with comorbidities such as muscle wasting that greatly increase mortality. Both acidosis and elevated glucocorticoids levels are hallmarks of CKD and implicated as having a synergistic role in driving muscle wasting. We investigated the synergistic effects of acidosis and the glucocorticoid cortisol on muscle metabolism and fibre size using ...

Introduction: Glucocorticoids are vital metabolic regulators. However, glucocorticoid excess (GE) causes severe metabolic dysfunction, ultimately leading to Cushing’s Syndrome. This dysfunction is often dependent on the presence of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Whether GE also alters metabolic rate, and whether this is also dependent on 11β-HSD1, remains unclear.Methods: Male and female wild-type (WT) ...

Background: Osteoporosis is a common feature of chronic kidney disease (CKD), associated with premature mortality. Glucocorticoids (GCs) are steroid hormones, that in excess, can drive the suppression of bone formation. We have shown that the glucocorticoid (GC) activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is dysregulated in CKD, where it may contribute to the suppression of bone formation. We utilised a murine model of CKD with...

Background: Skeletal muscle wasting is a characteristic feature of chronic kidney disease (CKD), associated with increased hospitalisations and premature mortality. Excess glucocorticoid signalling is a major contributor to the pathogenesis of muscle wasting in conditions of renal impairment. This study aimed to validate a murine model of CKD and utilise this to determine if deletion of 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) provides protec...

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...