Endocrine Abstracts

The central obese phenotype characteristic of Cushing's syndrome emphasises the role of glucocorticoids (GC) in regulating adipose tissue mass and distribution. We have shown that GCs stimulate adipocyte differentiation, but equally inhibit adipose stromal cell (ASC) proliferation. These effects are regulated at a pre-receptor level through 11beta-hydroxysteroid dehydrogenase type 1, but the 'post-receptor' signalling pathways remain unclear. To define novel GC targets in huma...

The most robust biochemical marker for the diagnosis of PCOS is hyperandrogenism (androstenedione, testosterone), thought to originate from the ovaries and/or adrenals. However the change in circulating androgen/LH ratios with increasing body mass in women with PCOS suggests the autocrine generation of androgens within adipose tissue itself. The enzyme 17beta hydroxysteroid dehydrogenase (17betaHSD) which has seven human isoforms is an important regulator of sex steroid metabo...

Insulin resistance and androgen excess are the cardinal features of polycystic ovary syndrome (PCOS). The severity of hyperandrogenism and metabolic dysfunction in PCOS are closely correlated, but underlying mechanisms remain poorly understood. Aldoketoreductase type 1C3 (AKR1C3) is an important source of adipose androgen generation, activating androstenedione to testosterone (T). We postulated that AKR1C3 plays a critical role linking androgen metabolism and...

Patients with GC excess (Cushing’s syndrome) develop central obesity, insulin resistance and hepatic steatosis. The A-ring reductases (5α-reductase type 1 (5αR1) and 2 (5αR2)) generate dihydrotestosterone from testosterone, but importantly also inactivate cortisol and are highly expressed in human liver. We propose that 5αR may regulate GC exposure and therefore may modulate metabolic phenotype in human liver.Primary human hepato...

Glucocorticoids (GCs) are prescribed for their anti-inflammatory and immunosuppressive properties. However, they have significant side-effects including a decline in muscle mass and function which has similarities to age related sacropaenia. Within skeletal muscle 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts 11-dehydrocorticosterone (11DHC) to active corticosterone (CORT) amplifying local GC action. We hypothesise that 11β-HSD1 mediated intramyoce...

Intra-abdominal adiposity is associated with insulin resistance and increased cardiovascular morbidity and mortality. Consequently, there is a need to identify factors involved in adipose tissue distribution. Patients with glucocorticoid (GC) excess develop a classic phenotype characterized by central, but not peripheral, obesity. Differences in gene expression between omental (om) and subcutaneous (sc) adipose tissue have been described, however, the molecular mechanisms unde...

Introduction: Real-time elastography (RTE) is a noninvasive ultrasound method of estimation of tissue stiffness by measuring the degree of local tissue displacements after a small compression. Recent data has shown indicate on its ability to differentiate benign and malignant tumors. The aim of the study was to evaluate the diagnostic accuracy of RTE in the diagnosis of malignant and benign thyroid nodules.Material and methods: A total of 75 thyroid nodu...

Intra-abdominal adiposity is associated with insulin resistance and increased cardiovascular morbidity and mortality. Differences in gene expression between omental (om) and subcutaneous (sc) adipose have been described, but molecular mechanisms underpinning differences in adipose biology are not known. Patients with glucocorticoid excess, Cushing’s syndrome, develop a phenotype characterized by central obesity. We have characterized the regulation of lipogenesis by gluco...

Glucocorticoid (GC) excess (Cushing’s syndrome) is characterized by central obesity, insulin resistance and in up to 20% of cases, non-alcoholic fatty liver disease (NAFLD). NAFLD is a progressive spectrum of disease ranging from hepatic steatosis to steatohepatitis, fibrosis and cirrhosis. Many processes contribute to lipid accumulation within heaptocytes including de novo lipogenesis which includes the rate-limiting carboxylation of acetyl CoA to malonyl-CoA by a...

In peripheral target tissues, levels of active glucocorticoid hormones are controlled by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which catalyses the reduction of cortisone to cortisol within the endoplasmic reticulum. For functional 11-ketoreductase activity, 11β-HSD1 requires the NADPH-generating enzyme hexose-6-phosphate dehydrogenase (H6PDH). Loss of 11-ketoreductase activity results in increased cortisol clearance and activation of the HPA axis wi...