Endocrine Abstracts

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...

Introduction: Muscle atrophy is a major clinical complication of acute exacerbations (AE) in chronic obstructive pulmonary disease (COPD). The enzyme 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) activates glucocorticoids (GCs) within muscle, is induced by inflammation, and has been shown to contribute towards GC-induced muscle wasting. In this study, we examined the role of 11β-HSD1 in this context using a murine model of COPD-AE in animals with transgenic globa...

G-protein coupled receptors (GPCRs) are transmembrane proteins whose surface expression and extracellular activation make them desirable drug targets. Approximately 35% of approved drugs target GPCRs, including osteoporosis treatments such as Teriparatide. Despite the ageing population resulting in increased osteoporosis diagnoses, current treatments lack long-term efficacy, highlighting the need to identify new drug targets. Using RNA-sequencing we identified multiple GPCR ge...

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...

In vitro data highlight a potential role for 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) in 11-oxygenated androgen biosynthesis, converting 11β-hydroxyandrostenedione (11OHA4) to 11-ketoandrostenedione (11KA4), the direct precursor of the potent androgen 11-ketotestosterone(11KT). As the kidney is the major site of HSD11B2 expression, we hypothesized that patients with chronic kidney disease (CKD) would have reduced 11-oxygenated androgen biosynthesis ...