Endocrine Abstracts

Colorectal cancer (CRC) is the third most common cancer and is one of the highest incidences and mortality tumours worldwide. Our group has previously shown that CRC favours oestradiol synthesis by increasing steroid sulfatase (STS) activity and altering 17β-hydroxysteroid dehydrogenases (HSD17Bs) expression. However, what regulates STS activity and HSD17Bs expression and activity in CRC remains unknown. In breast and prostate cancer inflammatory mediators, such as TNF&#9...

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...

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 are highly detrimental to skin integrity and function both when used locally for anti-inflammatory treatments and during conditions of raised systemic concentrations such as Cushing’s syndrome. Many of the adverse effects of glucocorticoids on skin are also symptoms associated with natural intrinsic aging and extrinsic photoaging.Locally, glucocorticoid availability is regulated independently of circulating levels by 11β-hydroxy...

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...

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by progressive joint destruction and inflammatory activation and hyperproliferation of synoviocytes. We have previously reported a marked shift towards reduced local androgen metabolism in active RA, driven by changing expression of SRD5A1 and AKR1C3 within macrophages. In this study we examined the role of altered androgen metabolism and availability in the inflammatory function of both macr...