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...

With an aging population the number of total joint replacements performed due to end-stage osteoarthritis is increasing. Critically, a significant proportion of patients report dissatisfaction following surgery, with around 10% of hip and 20% of knee OA patients developing chronic postoperative pain. Obesity is a well-known risk factor for the development of OA. Pre-surgical obesity has been previously associated with worse clinical outcomes following arthroplasty. Therefore, ...

Background: Our practice is to commence newly diagnosed children and young people (CYP) with diabetes, over 5 years old, on multiple daily insulin (MDI), using fixed Insulin to Carbohydrate ratios (ICRs) with meals across the day. ICRs are subsequently adjusted according to blood glucose response, individualising insulin treatment. We know intensified insulin therapy includes use of varied ICRs, reflecting varying insulin sensitivity at different times of day. We do not know w...

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...

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...