Endocrine Abstracts

Excessive glucocorticoid exposure has been implicated in the pathogenesis of obesity and the metabolic syndrome. The in vivo conversion of inactive to active glucocorticoids is catalysed by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), requiring NADPH as a cofactor. Hexose-6-phosphate dehydrogenase (H6PDH) is co-localised with 11β-HSD1 in the lumen of the endoplasmic reticulum and controls local NADPH availability. Thus H6PDH plays an important role...

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 excess, Cushing's syndrome, is a recognised cause of insulin resistance and in some cases diabetes mellitus. In addition, patients develop reversible central obesity. However, the exact mechanisms that underpin the development of glucocorticoid mediated insulin resistance and central obesity are not known. We have hypothesized that at a cellular level, the tissue specific generation of cortisol from inactive cortisone through the action of 11beta-hydroxysteroid ...

Glucocorticoids (GCs) mediate many of their physiological effects through inhibition of cell proliferation. More contentious is the antiproliferative action of GCs and their possible tumour-modifying effects in neoplastic tissues. However, in recent studies we have shown that 'prereceptor' metabolism of GCs by the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) is a pivotal determinant of cell proliferation and tumour formation. Two isozymes of 11beta-HSD interconvert ...

Interferon therapy for chronic hepatitis C infection has been associated with thyroid abnormalities. We sought to characterise the incidence of this in a cohort of treated hepatitis C patients receiving weekly pegylated interferon therapy in a tertiary Hepatology unit. Patients were scheduled to receive 24 or 48 weeks treatment with monthly thyroid function tests (TFTs). Data was collected from electronic treatment records of 154 consecutive patients and analysed by a single i...

The physiological effects of glucocorticoids (GCs) are, at least in part, mediated by an inhibition of cell proliferation. More contentious is their anti-proliferative action and possible tumour modifying effects in neoplastic tissues. Central to the action of GCs in target tissues is the expression and function of two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) that serve to interconvert active cortisol (F) and inactive cortisone (E). 11beta-HSD type 1 (11bet...