Searchable abstracts of presentations at key conferences in endocrinology

ea0019p122 | Diabetes, Metabolism and Cardiovascular | SFEBES2009

Effect of green coffee bean extract and chlorogenic acid consumption on 11βHSD activity in humans and mice

Almoosawi S , Dickinson A , Fyfe L , Kenyon CJ , Al-Dujaili EAS

Increased 11β hydroxysteroid dehydrogenase type 1 (11βHSD1) activity is implicated in the development of the metabolic syndrome. Identifying natural compounds that influence 11βHSD1 activity could lead to novel methods of treating obesity, cardiovascular disease and diabetes. In the present study, we tested the effect of green coffee bean extract (GCBE), rich in chlorogenic acid (CGA), in human volunteers and of CGA in mice on blood pressure (BP), lipid and gluc...

ea0015p301 | Steroids | SFEBES2008

Development and validation of highly sensitive and specific enzyme immunosorbant assays for deoxycorticosterone and corticosterone: application to urine samples from cyp11b1 knockout mice

Al-Dujaili Emad AS , Kenyon CJ , Mullins LJ , Mullins JJ

Deoxycorticosterone (DOC: a weak mineralocorticoid) is the precursor to corticosterone (B: the major glucocorticoid in rodents) and aldosterone. Cyp11b1 encodes 11β-hydroxylase which catalyses the conversion of DOC to B in rodents. The aim of this study is to develop sensitive and specific ELISA methods to estimate urinary DOC and B levels in mice. Antibodies against DOC and B were raised in rabbits by our laboratories as previously described and HRP-Goat anti-Rabbit IgG ...

ea0015p302 | Steroids | SFEBES2008

Development and validation of a highly sensitive and specific enzyme immunosorbant assay for aldosterone: application to urine samples from cyp11b1 knockout mice

Al-Dujaili Emad AS , Kenyon CJ , Mullins LJ , Mullins JJ

The majority of immunoassays used to measure aldosterone (most potent mineralocorticoid) levels are still based on radio-iodinated tracer, lack sensitivity and specificity and there is a definite need for their improvement. The aim of this project is to develop a highly sensitive and specific ELISA method for urinary aldosterone estimation in samples obtained from wild type and cyp11b1 knockout mice. Antibodies against aldosterone were raised in sheep as previously described. ...

ea0011oc27 | Diabetes and metabolism | ECE2006

A selective increase in adipose 11β-HSD1 expression in corticosterone-treated Pomc null mice is associated with development of metabolic syndrome

Michailidou ZM , Coll APC , Morton NMM , Kenyon CJ , O’Rahilly S , Seckl JR , Chapman KE

Inactivating mutations of the POMC gene in humans and mice result in a complex phenotype of hyperphagia, obesity and glucocorticoid (GC) deficiency, but without many features of metabolic syndrome. We have previously shown that replacement of GC in Pomc−/− mice exacerbates their hyperphagia, increases fat mass and elevates plasma leptin and insulin. We have now examined key determinants of glucocorticoid action, including glucocorticoid receptor (...

ea0011p345 | Diabetes, metabolism and cardiovascular | ECE2006

Adipose glucocorticoid synthesis: transcription of the 11β-hydroxylase gene in omental but not subcutaneous adipose tissue

MacKenzie SM , Kenyon CJ , Livingstone DEW , Andrew R , Fraser R , Connell JMC , Davies E

The major glucocorticoids (cortisol in man and corticosterone in the rat) play an important role in obesity and its attendant hypertension. However, there is no consistent evidence of glucocorticoid excess in simple obesity, suggesting that its role in the regulation of adipose tissue mass results from a more complex mechanism than adrenal hypersecretion of glucocorticoid. Glucocorticoid biosynthesis is not limited to the adrenal cortex; mRNA and enzymatic activity of 11β...

ea0011p385 | Diabetes, metabolism and cardiovascular | ECE2006

Dietary regulation of peripheral glucocorticoid action: comparison of saturated and unsaturated fats

Man TY , Ramage L , Gokcel A , Michailidou Z , Kenyon CJ , Chapman K , Seckl JR , Morton NM

Obesity/Metabolic syndrome (insulin resistance, hypertension, cardiovascular disease) has reached epidemic levels in western societies. Aberrantly elevated glucocorticoid amplification by intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) within adipose tissue might explain the striking similarities between idiopathic obesity/metabolic syndrome and Cushing’s syndrome, causes by plasma GC excess. A major contributor to obesity/metabol...

ea0011p397 | Diabetes, metabolism and cardiovascular | ECE2006

Dietary potassium driven responses in the renal WNK kinase pathway in vivo

O’Reilly M , Marshall E , MacGillvray T , Mittal M , Kenyon CJ , Brown RW

WNK1 (With-No-K, lysine) and WNK4 are serine/threonine kinases, mutated in Gordon syndrome (Pseudohypoaldosteronism Type II), a dominant, hypertensive, hyperkalaemic disorder; implicating this novel WNK pathway in normal regulation of blood pressure (BP) and electrolyte balance. Previous Xenopus oocyte work implicates WNK4 in regulation of K+ secretion via ROMK (renal outer medullary K+ channel) and Cl- transport pathways both paracellularly via tight junctions (claudin...

ea0011p399 | Diabetes, metabolism and cardiovascular | ECE2006

Adrenocortical function in obese Zucker rats

Kenyon CJ , Livingstone DEW , McNeilly AD , Davies E , Andrew R , MacKenzie SM

Adrenal steroids and alterations in steroid metabolism are important factors in the development of obesity in Zucker rats. One might predict, therefore, that the function of the adrenal gland differs between lean and obese Zucker animals. Accordingly, we investigated adrenal gland morphology and function and have considered not only glucocorticoids and HPA activity but also the renin-angiotensin-aldosterone system. Plasma samples and adrenal glands were obtained from young 12 ...

ea0011p752 | Steroids | ECE2006

Alterations in Scavenger Receptor B1 and steroidogenic enzymes within the adrenal gland in response to dietary bile acids

McNeilly AD , Livingstone DEW , MacKenzie SM , Davies E , Kenyon CJ , Walker BR , Andrew R

Bile acids inhibit glucocorticoid and mineralocorticoid metabolism. However bile acids may also influence hormone action by modulating steroidogenesis in the adrenal gland. In rodents adrenal cholesterol supply for steroidogenesis is derived from circulating HDL through the actions of scavenger receptor SR-B1. Since hepatic SR-B1 expression is known to be regulated by bile acids, we have investigated whether adrenal SR-B1 is similarly affected and, if so, whether adrenal lipid...

ea0015p303 | Steroids | SFEBES2008

Mechanisms of altered glucocorticoid metabolism and adrenal insufficiency in cholestatic liver disease

McNeilly AD , Livingstone DEW , McKenzie SM , Davies E , Skott O , Thiesson H , Kenyon CJ , Walker BR , Andrew R

Glucocorticoids mediate the stress response, regulated via the hypothalamic–pituitary–adrenal (HPA) axis. The HPA axis is down-regulated and its responsiveness to stress is impaired in cholestasis. The mechanisms are unknown, but may involve reduced glucocorticoid clearance. Hepatic 5beta-reductase is involved in glucocorticoid inactivation and bile acid biosynthesis. We showed previously that bile acids are potent competitive inhibitors and transcriptional regulator...