Endocrine Abstracts

Polycystic ovary syndrome (PCOS) is a clinical triad of anovulation, insulin resistance, and androgen excess in women. Adipose androgen generation of testosterone from androstenedione by aldo-ketoreductase type 1C3 (AKR1C3) may contribute to hyperandrogenism, particularly in the setting of obesity. We aimed to determine the effects of BMI and age on AKR1C3 expression in subcutaneous (SC) and omental (OM) fat depots in both women and men.Paired SC and OM ...

Introduction: AKR1D1 is a 5β-reductase that sits at the interface of steroid hormone metabolism and primary bile acid biosynthesis. 5β-reduced androgens are widely believed to be inactive, but to our knowledge there are currently no data that have directly tested their ability to activate the androgen receptor (AR). We therefore wanted to test the ability of AKR1D1 to regulate androgen availability in vitro and to determine if 5β-reduced androgens are a...

Patients with glucocorticoids (GC) excess develop central obesity, insulin resistance and hepatic steatosis in up to 20% of cases. Current dogma suggests that GCs cause insulin resistance in all tissues. However, we have previously demonstrated that GCs induce insulin sensitisation in adipose tissue in vitro, whilst causing insulin resistance in skeletal muscle. In rodent hepatocytes, GCs enhance insulin stimulated lipogenesis but studies in human hepatocytes have not...

The potent effects of glucocorticoids (GCs) upon carbohydrate metabolism are well described. However, their actions upon lipid metabolism are poorly characterized. Patients with GC excess (Cushing’s syndrome) develop central obesity, insulin resistance and hepatic steatosis in up to 20% of cases. The A-ring reductases (5α-reductase type 1 [5αR1] and type 2 [5αR2]), inactivate cortisol as well as generate dihydrotestosterone (DHT) from testosterone (T) and a...

Harvey Cushing’s work informed us of the deleterious consequences of circulating cortisol excess – hypertension, osteoporosis and obesity that contributes to diabetes and premature mortality. Conversely, Hench, Kendall and Reichstein were Nobel Laureates in Physiology 1950 for the discovery of cortisone and demonstrating efficacy in patients with Rheumatoid Arthritis – in effect the birth of the anti-inflammatory actions of glucocorticoids.<p class="abstext"...

Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Although there is a strong inverse correlation between intramuscular triglyceride (IMTG) levels and insulin sensitivity, the impact of glucocorticoids upon the processes that regulate skeletal muscle lipid metabolism has not been explored.Mouse C2C12 skeletal myocytes were grown to confluence and differentiated into myotubes in chemically defined medi...

Patients with glucocorticoid (GC) excess, Cushing’s syndrome, develop a classical phenotype characterized by insulin resistance and central obesity. Whilst it is clear that GCs are essential for adipocyte differentiation, their impact upon many of the processes that regulate lipid accumulation has not been explored in detail. De novo lipogenesis involves carboxylation of acetyl CoA to malonyl-CoA by acetyl CoA carboxylase (ACC), which is subsequently converted to p...

Glucocorticoid (GC) excess is characterized by central obesity, insulin resistance and in some cases, type 2 diabetes mellitus. Whilst it is accepted that GCs cause insulin resistance, both insulin and GCs act synergistically to promote adipocyte differentiation. We have previously shown that acute treatment (24 h) with GCs enhances insulin signalling in human adipocytes. We hypothesise that the generation of cortisol from inactive cortisone by 11β-hydroxysteroid dehydrog...

The epidemic of obesity, insulin resistance and type 2 diabetes has heightened the need to understand the mechanisms that contribute to their pathogenesis. Endogenous glucocorticoid (GC) production and metabolism have been implicated based upon parallels with Cushing’s syndrome. The interaction between GC metabolism and insulin sensitivity in the context of significant weight loss has not been explored. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that gen...

Intra-abdominal adiposity is associated with insulin resistance and increased cardiovascular morbidity and mortality. Obesity occurs as a consequence of increased adipocyte size (hypertrophy) and number (differentiation or hyperplasia). Whilst differences in gene expression between omental (om) and subcutaneous (sc) adipose tissue have been described, the molecular mechanisms that underpin the differences in adipose tissue biology and the depot specific metabolic risks that th...