Endocrine Abstracts

The prevalence of obesity and its association with many health complications have evoked a high interest in adipose tissue metabolism. In man, glucocorticoid (GC) excess increases fat mass and the risk of developing Metabolic Syndrome. The enzyme responsible for modifying intracellular GC concentrations in adipose tissue is 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The aim of this study was to characterise the novel human preadipocyte cell line (Chub-S7) an...

Without adequate treatment patients with acromegaly die prematurely from cardiovascular disease (CVD); however the contribution of atherosclerosis in this process is controversial. Increased carotid IMT is an early morphological marker of atherosclerosis and predictor of subsequent cardiovascular events. Contradictory data exist regarding IMT in patients with acromegaly.We measured carotid IMT in 79 patients with acromegaly (47 male, mean age 55±14 ...

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 ...

Prostanoids have been elucidated as potent adipogenic hormones. Cyclooxygenase (PTGS) is the rate-limiting enzyme of prostanoid biosynthesis and its product, prostaglandin (PG) H2 is a precursor of PGE2, PGF2, PGD2 and PGI2. PGH2 is also metabolised by prostaglandin D-synthase (PTGDS) to PGD2 which spontaneously converts to PGJ2 or can be enzymatically converted to PGF2alpha by AKR1C3. These two metabolites have opposite effect on adipogenesis; PGF2alpha is a PPARgamma antagon...

Glucocorticoid excess results in central obesity and insulin resistance/diabetes mellitus. At a pre-receptor level, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) modulates glucocorticoid levels and has been implicated in the pathogenesis of the metabolic syndrome. 11beta-HSD1 is a bi-directional NADP(H) dependant enzyme, but keto-reductase activity predominates in-vivo. Recent studies indicate that the enzyme H6PDH ensures reductive metabolism (cortisone to c...

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has been implicated in the pathogenesis of human obesity and insulin resistance through 11-oxoreductase activation of cortisone (E) to cortisol (F) within the endoplasmic reticulum (ER) of adipocytes and hepatocytes. In its purified state 11beta-HSD1 is principally a dehydrogenase, converting F to E. Oxo-reductase activity can be regained by the addition of an NADPH regeneration system. In vivo hexose-6-phosphate ...

Glucocorticoids are an important adipogenic factor. In man, circulating cortisol excess causes visceral obesity, but in simple obesity glucocorticoid levels are usually normal. However, in adipose tissue cortisol availability to bind to the glucocorticoid receptor (GR) is modulated by 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1). Human preadipocytes display both dehydrogenase (cortisol to cortisone) and oxo-reductase (cortisone to cortisol) activity. Recent genet...

The global epidemic of obesity has heightened the need to understand the mechanisms that underpin its pathogenesis. Clinical observations in patients with Cushing's syndrome have highlighted the link between cortisol and central obesity. However, whilst circulating cortisol levels are normal or reduced in obesity, local regeneration of cortisol, from inactive cortisone, by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has been postulated as a pathogenic mechanism. W...

Increased mortality in patients with acromegaly has been confirmed in a number of retrospective studies, but causative factors and relationship to serum IGF1 remain uncertain. The West Midlands Acromegaly database contains details of 419 patients (178 males). Serum IGF1 data from the Regional Endocrine Laboratory was available for 338 patients (81%). At diagnosis mean age was 47 years (range 12-84) and mean GH was 70plus/minus5.4 milliunits per litre. 61% were treated by surge...

To dissect mechanisms which result in 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) insensitivity we have compared the antiproliferative actions of 1,25(OH)2D3 in a range of malignant breast cell lines (ZR-75-1, T-47D, MCF-7, MCF-7Res and MDA-MB-231) and the non-malignant breast epithelial cells MCF-12A cells. All the malignant cell lines displayed greater resistance than MCF-12A cells to 1,25(OH)2D3. For ex...