Searchable abstracts of presentations at key conferences in endocrinology

ea0002sp9 | The Endocrinology of Syndrome X | SFE2001


Walker B

In Cushing's Syndrome, elevated circulating cortisol levels are responsible for the association of central obesity, hypertension, insulin resistance, hyperglycaemia, and dyslipidaemia. Recent evidence suggests that there are subtle elevations in circulating cortisol concentrations amongst patients with hypertension and insulin resistance, and these are predicted by low birthweight suggesting that they may be programmed by events occurring in early life. In addition, there is e...

ea0009oc28 | Oral Communication 4: Steroids | BES2005

Impact of dietary chenodeoxycholic acid on the hypothalamic-pituitary-adrenal axis in rats

McNeilly A , Walker B , Andrew R

Alterations in the rate of glucocorticoid(GC) metabolism induce compensatory changes in GC secretion under the control of the hypothalamic-pituitary-adrenal (HPA) axis. The principal routes of metabolic clearance of GCs are by hepatic A-ring reduction however the regulation of these enzymes is poorly understood. Recently we and others have demonstrated that bile acids act as potent inhibitors of GC metabolism by 5beta-reductase and 11beta-hydroxysteroid dehydrogenases in vi...

ea0019p136 | Diabetes, Metabolism and Cardiovascular | SFEBES2009

Susceptibility to hyperinsulinaemia and fatty liver with loss of 5alpha-reductase 1 occurs in rats and mice and is not androgen dependent

Livingstone D , Walker B , Andrew R

5alpha-Reductase 1 (5aR1) catalyses A-ring reduction of glucocorticoids and androgens. We previously demonstrated that transgenic disruption of 5aR1 predisposes male mice to fatty liver and insulin resistance when challenged with a high-fat diet. Here, we have dissected the contributions of androgens and glucocorticoids to the metabolic phenotype using 2 models of enzyme inhibition (trangenesis and pharmacology).Female 5aR1−/− mice (KO) and w...

ea0009p141 | Steroids | BES2005

Chronic glucocorticoid excess does not cause fatty liver disease in mice

Raubenheimer P , Nyirenda M , Walker B

Case reports in humans implicate glucocorticoid (GC) excess, through exogenous administration or endogenous overproduction, as a cause of non-alcoholic fatty liver disease. In rodents, massive doses of GCs have induced fatty liver when liver fat was measured in the fasting state. The mechanisms through which GCs might induce fatty liver are unknown, but are thought to be secondary to insulin resistance/hyperinsulinaemia. In this study, we examined the effect of dexamethasone (...

ea0007p40 | Diabetes, metabolism and cardiovascular | BES2004

Understanding the fetal origins of the metabolic syndrome and its amplification by obesity; high fat feeding potentiates the programming of hepatic insulin resistance by antenatal dexamethasone in rats

Drake A , Raubenheimer P , Seckl J , Walker B

Mechanisms underlying the association of low birth weight with the metabolic syndrome in adults remain poorly understood. Epidemiological studies suggest that obesity is not programmed by early life events, but amplifies the risks of intra-uterine growth retardation. We have explored the effects of dietary obesity in rats in which features of the metabolic syndrome have been programmed by prenatal dexamethasone.16 pregnant Wistar rats were treated with d...

ea0007p204 | Steroids | BES2004

Inhibition of steroid 5beta-reductase by bile acids

McNeilly A , Livingstone D , Walker B , Andrew R

Hepatic A-ring reduction of glucocorticoids is enhanced in obesity, perhaps contributing to compensatory activation of the hypothalamic-pituitary-adrenal axis and adrenal androgen excess. One pathway activated is the formation of tetrahydro metabolites by two sequential steps catalysed by 5beta-reductase (5bR) followed by 3alpha-hydroxysteroid dehydrogenases (3HSD). However, regulation of these enzymes is understood poorly. 5bR and 3HSD are also involved in the conversion of c...

ea0007p213 | Steroids | BES2004

Local regeneration of glucocorticoids by 11betaHSD-1 within the vessel wall modulates angiogenesis

Small G , Dover A , Hadoke P , Walker B

Angiogenesis, which is tightly regulated in health and disturbed in many diseases, is inhibited by glucocorticoids. Local glucocorticoid availability within the vessel wall is determined by the pair of enzymes 11beta-hydroxysteroid dehydrogenase type 1 and 2 (11HSD-1 and 2) that catalyse the interconversion of active glucocorticoid (corticosterone in mice, cortisol in humans) with inactive 11-dehydrocorticosterone or cortisone. We hypothesized that regeneration of active gluco...

ea0005oc9 | Cardiovascular Endocrinology | BES2003

Use of glucocorticoids and risk of cardiovascular disease in a population-based cohort study of 164,133 participants

Wei L , MacDonald T , Walker B

Context: Glucocorticoids have adverse systemic effects which may predispose to cardiovascular disease. The effect of glucocorticoid use on cardiovascular disease has not been assessed.Objective: To test the hypothesis that users of exogenous glucocorticoids have a dose-dependent increased risk of cardiovascular disease; in particular, that supraphysiological doses will be associated with cardiovascular disease.Design: A cohort study using a record linkage database....

ea0003oc25 | Metabolism | BES2002

Programming of adult adipose tissue metabolism by prenatal glucocorticoids in the rat

Cleasby M , Walker B , Seckl J

Prenatal dexamethasone (dex) administration in rats retards foetal growth, and programmes hyperinsulinaemia and glucose intolerance in adult offspring. This can be explained in part by increased hepatic gluconeogenesis, due to up-regulated glucocorticoid receptor (GR) expression, but may also involve impaired peripheral glucose disposal. In this model, we previously showed no increase in skeletal muscle GR, and have now examined GR and key metabolic genes in adipose tissue.</...

ea0019oc13 | Neuroendocrine and Steroids | SFEBES2009

Inhibition of 11β-hydroxysteroid dehydrogenase type 1 promotes intra-retinal vascularisation in a murine model of ischaemic retinopathy

Dover A , Stitt A , McVicar C , Kitson C , Hadoke P , Walker B

Glucocorticoids possess potent angiostatic properties. 11β-Hydroxysteroid dehydrogenase type 1 (11βHSD1) amplifies local glucocorticoid action in a tissue-specific manner, and we have shown that inactivation of this enzyme enhances angiogenesis within sponges implanted subcutaneously, wounds and infarcted myocardium. 11βHSD1 is present within ocular tissues but its role in the pathogenesis of proliferative retinopathy is unknown. We hypothesised that inhibition ...