Searchable abstracts of presentations at key conferences in endocrinology

ea0019p143 | Diabetes, Metabolism and Cardiovascular | SFEBES2009

Increased mineralocorticoid activity in obese Zucker rats is independent of the renin–angiotensin system and hepatic steroid metabolism.

Kenyon C , Livingstone D , Ingram M , Al-Dujaili E , Rutter A , Fraser R , Andrew R

Hypertension in obese Zucker rats is associated with raised plasma aldosterone, suppressed renin and increased hypothalamo–pituitary–adrenal activity. We investigated the possible causes and consequences of these associations by comparing adrenal gene expression and urinary electrolyte and steroid excretion patterns in lean and obese rats. Groups (n=11) of adult male lean and obese Zucker rats were held in metabolism cages for 7 days. Urine collected over the ...

ea0012s34 | Adipocyte tissue and insulin resistance | SFE2006

The ins and outs of steroid hormones in human adipose tissue

Walker BR , Andrew R

Several enzymes are expressed in adipose tissue which catalyse interconversion of steroids, generating oestrogens (aromatase), androgens (5α-reductase 1), and glucocorticoids (11β-HSD1). These steroids may activate local receptors which influence body fat accumulation and distribution, or be secreted to exert endocrine effects. Several mouse models (e.g. aromatase and 11β-HSD1 knockout mice and studies with 11β-HSD1 inhibitors) illustrate the potential impo...

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...

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...

ea0019p155 | Diabetes, Metabolism and Cardiovascular | SFEBES2009

7-Oxysterols are metabolised by 11ß-hydroxysteroid dehydrogenase-1 within the aortic wall but do not directly influence contractility

Mitic T , Walker BR , Andrew R , Hadoke PWF

Recent investigations have suggested that 11ß-hydroxysteroid dehydrogenase-1 (11ßHSD1) activity influences development of atherosclerotic lesions and that pharmacological inhibition of this enzyme may have therapeutic benefits. Whilst these findings have been attributed to glucocorticoid metabolism, 11ßHSD1 also inter-converts 7-oxysterols (oxidized products of cholesterol which may promote atherogenesis). This study investigates whether metabolism of 7-oxystero...

ea0019p327 | Steroids | SFEBES2009

Measuring cortisone production in man using a new stable isotope tracer

Hughes K A , Reynolds R M , Andrew R , Walker B R

Background: 11β-hydroxysteroid dehydrogenases (11β-HSD1&2) interconvert cortisol (F) and cortisone (E). Although 11β-HSD1 reductase activity has been measured in vivo, E production (dehydrogenase activity) has not been quantified using a Gold Standard technique, steady state tracer infusion.Aim: To develop a method to measure E production in vivo using the stable isotope tracer d2-cortisone (d2E).Me...

ea0011p387 | Diabetes, metabolism and cardiovascular | ECE2006

Androgen regulation of hepatic glucocorticoid metabolism in obese Zucker rats

Livingstone DEW , Barat P , McDonnell CR , Walker BR , Andrew R

Obesity is associated with decreased hepatic reactivation of glucocorticoids (Gc) by 11β-hydroxysteroid dehydrogenase type 1 (11HSD) and increased metabolism of glucocorticoids by hepatic A-ring reductases, which may contribute to activation of the hypothalamic-pituitary-adrenal axis. Androgen action encourages central obesity and increased metabolic complications, possibly by altering Gc metabolism.This study investigates the role of gonadal androg...

ea0007p254 | Clinical case reports | BES2004

Puerperal hypoglycaemia in a young woman with type 1 diabetes mellitus

Moisey R , Andrew J , Nagi D , Jenkins R

A 30-year-old woman with long standing type 1 diabetes presented with recurrent severe hypoglycaemia. One month earlier she had given birth to her first child. Before pregnancy her HbA1c had been 7.8 to 9.2 percent (RR 3.1 to 5.0 percent) but improved by the third trimester to 6.8 percent. Before pregnancy her total daily insulin dose was 50 units and by the third trimester it had only increased by 25 percent to 60 units. The pregnancy and birth were uneventful with no hypogly...

ea0005p81 | Diabetes, Metabolism and Cardiovascular | BES2003

Effects of the 11beta hydroxysteroid dehydrogenase inhibitor carbenoxolone on insulin sensitivity in human obesity

Sandeep T , Andrew R , Homer N , Walker B

Inhibiting 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1) has been proposed to prevent local regeneration of cortisol from cortisone, and thus enhance hepatic and adipose insulin sensitivity. In healthy men and patients with type 2 diabetes, the non-selective 11HSD inhibitor carbenoxolone enhances hepatic insulin sensitivity but, paradoxically, does not increase peripheral glucose disposal. In obesity, 11HSD1 activity and mRNA are increased in adipose biopsies. We tested ...