Searchable abstracts of presentations at key conferences in endocrinology

ea0019p305 | Steroids | SFEBES2009

Differences in aldosterone synthase and 11β-hydroxylase genes between Caucasian and Afro-Caribbean hypertensive families

Alvarez-Madrazo S , Padmanabhan S , Friel E , McKenzie C , Keavney B , Davies E , Connell J

Aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) genes are highly homologous in their coding regions (95%), lie in tandem approximately 40kb apart in human chromosome 8, and may have arisen from gene duplication. The pattern of linkage disequilibrium (LD) of this region in a population is determined not only by the distribution of recombination events but also by demographic factors determining the amount of random genetic drift. There is suggestiv...

ea0019p321 | Steroids | SFEBES2009

MicroRNA: a novel post transcriptional regulator of 11β-hydroxlase (CYP11B1) and aldosterone synthase (CYP11B2)

Wood S , Forbes G , MacKenzie S , Stewart P , Connell J , Davies E

The corticosteroids aldosterone and cortisol are implicated in the aetiology of hypertension. The CYP11B1 and CYP11B2 genes encode 11β-hydroxlylase and aldosterone synthase; polymorphisms across the CYP11B1/B2 locus are associated with increased aldosterone production, inefficient 11β-hydroxlation and hypertension. While polymorphisms located in the promoter region of both genes may alter transcription factor binding, other variants located in th...

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...

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 ...

ea0011p744 | Steroids | ECE2006

Endogenous corticosteroid synthesis in subjects after bilateral adrenalectomy

Freel M , Fraser R , Ingram M , Davies E , Wallace M , Connell J

Corticosteroids can be synthesised in tissues other than the adrenal cortex but the contribution of this extra-adrenal corticosteroidogenesis to circulating levels in man is not known. We studied this in a group 10 subjects taking chronic glucocorticoid replacement following bilateral adrenalectomy. In phase 1, they were maintained on cortisol alone (30 mg/day). In phase 2, cortisol was replaced by dexamethasone (2 mg/day) and in phase 3, they received both cortisol and dexame...

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...

ea0009p134 | Steroids | BES2005

Haplotype analysis of the aldosterone synthase (CYP11B2) and 11beta-hydroxylase gene (CYP11B1) locus

Barr M , Wilkinson D , Freel E , MacKenzie S , Brain N , Fraser R , Davies E , Connell J

We have shown that linked polymorphisms in the aldosterone synthase gene (CYP11B2) are associated with hypertension and altered aldosterone production. However, the most consistent intermediate phenotype associated with this genetic variation is increased plasma 11-deoxycortisol (S) and urinary excretion of its metabolite, tetrahydrodeoxycortisol (THS); this is paradoxical as S is a substrate for the enzyme 11beta-hydroxylase, encoded by the neighbouring gene, CYP11B1. However...

ea0007p206 | Steroids | BES2004

Regulation of 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) gene expression in the rat adrenal gland and central nervous system by ACTH and dexamethasone

Ye P , Kenyon C , Nichol K , MacKenzie S , Fraser R , Seckl J , Connell J , Davies E

11Beta-Hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) catalyse the synthesis of corticosterone and aldosterone respectively in the rat adrenal cortex. Recent studies have shown that CYP11B1 and CYP11B2 are also expressed in the central nervous system (CNS) but little is known about their regulation. In this study, we have quantified CYP11B1 and CYP11B2 gene expression in the CNS following treatment with ACTH and dexamethasone.Three groups of ma...

ea0007p209 | Steroids | BES2004

The effect of adrenalectomy on 11beta-hydroxylase(CYP11B1) and aldosterone synthase (CYP11B2) gene expression in the hippocampus

Ye P , Kenyon C , Nichol K , MacKenzie S , Fraser R , Seckl J , Connell J , Davies E

11Beta-Hydroxylase and aldosterone synthase catalyse the synthesis of corticosterone and aldosterone in the rat adrenal cortex and are encoded by the CYP11B1 and CYP11B2 genes respectively. These genes are also expressed in distinct regions of the CNS and cardiovascular system where they may play a key role in behavioural response and blood pressure homeostasis. However, it is unclear whether this extra-adrenal expression is regulated by, or contributes to, circulating levels ...

ea0005p223 | Steroids | BES2003

Excretion of the urinary metabolite of deoxycortisol is heritable and influenced by polymorphic variation at the CYP11B2 (aldosterone synthase) locus

Myosi B , Keavney B , Watkins H , Davies E , Ingram M , Fraser R , Connell J

Background: The enzymes 11beta-hydroxylase and aldosterone synthase are key control steps in regulation of cortisol and aldosterone synthesis. We have previously reported that polymorphic variation of the gene encoding aldosterone synthase (CYP11B2) is associated with altered efficiency of 11b-hydroxylation of the precursor of cortisol, deoxycortisol. In order to examine this relationship in greater detail, we have studied the pattern of steroid precursor metabolite excretion ...