Searchable abstracts of presentations at key conferences in endocrinology

ea0011p749 | Steroids | ECE2006

Hydrocortisone replacement therapy- the controversy continues…

Freel M , Thomson A , Devers M , Campbell K , Grant D , Wallace M , Connell J

Although hydrocortisone is the standard replacement therapy for primary or secondary adrenal insufficiency (AI), there are limited data on dosage requirements and the value of salivary monitoring in this patient group. We assessed inter-individual variability in cortisol metabolism and relationships between plasma and salivary cortisol profiles in 27 patients. Ten (3 male) patients had primary AI and 17 (8 male) secondary AI. Salivary and plasma cortisol levels were measured a...

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...

ea0008p87 | Steroids | SFE2004

Variability in Hydrocortisone Pharmacokinetics Following Intravenous and Oral Administration in Patients with Adrenal Insufficiency

Devers MC , Thomson AH , Freel M , Grant D , Campbell K , Wallace M , Connell JMC

Hydrocortisone is the standard replacement therapy in patients with primary or secondary adrenal insufficiency (AI) but there is no current consensus on the most appropriate replacement dose and the extent to which this varies between individuals. This study examines inter-individual variability in cortisol metabolism in patients taking hydrocortisone therapy and investigates the relationship between plasma and salivary concentrations.Subjects and Method...

ea0007p46 | Diabetes, metabolism and cardiovascular | BES2004

Single nucleotide polymorphisms within oxidative stress genes affect arterial compliance: gene function relationships

Drummond R , Brosnan M , Tan C , Kirk A , Hamilton C , Connell J , Dominiczak A

Background and Hypothesis:- A common NOS3 Single nucleotide polymorphisms (SNP) (894 G/T) which encodes a Glu298Asp amino acid substitution in endothelial NO synthase has been associated with cardiovascular disorders in which NO bioactivity is impaired. The gene coding for p22phox, a critical component of the NADH/NAD(P)H oxidase enzyme system, a major source of vascular SO, is CYBA. Among the allelic polymorphisms reported in CYBA is C242T, associated wit...

ea0007p199 | Steroids | BES2004

Glucocorticoids contribute to the heritability of leptin in Scottish adult female twins

Wallace A , Banfield E , Ingram M , Swan L , Hillis W , Connell J

There is considerable evidence to indicate that the hypothalamic-pituitary-adrenal axis is activated in obesity and that glucocorticoids may have a stimulatory effect on adipocyte leptin production. However, the precise interactions between glucocorticoids and leptin are complex and remain poorly understood. To investigate whether the glucocorticoid/leptin interaction is affected by genetic factors, we investigated the heritability of BMI, leptin and glucocorticoid metabolite ...

ea0007p201 | Steroids | BES2004

The origin of 18-hydroxycortisol and 18-oxocortisol in man

Freel E , Shakerdi L , Wallace A , Ingram M , Fraser R , Connell J

18-hydroxycortisol (18-OHF) and 18-oxocortisol (18oxo-F) are derivatives of cortisol whose origin and regulation are uncertain. 18-OHF is synthesised by zona fasciculata 11-beta hydroxylase; 18-oxoF can only be produced by zona glomerulosa aldosterone synthase. Levels of both steroids are increased in patients with Primary Aldosteronism. However, the origin of these steroids in normal subjects is not known.8 normal subjects and 6 subjects with primary adrenal failure performed...

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 ...

ea0005p229 | Steroids | BES2003

Regulation of aldosterone synthase (CYP11B2) gene expression in the rat adrenal gland and central nervous system by sodium and angiotensin II

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

Aldosterone synthase catalyses the synthesis of aldosterone in the adrenal cortex and is encoded by the CYP11B2 gene. Recent studies have shown that CYP11B2 is also expressed in the central nervous system (CNS) but little is known about its regulation. In this study, we have quantitated CYP11B2 expression in the CNS following dietary manipulation of sodium and infusion of angiotensin II.In study 1, 3 groups of male WKY rats (n=6) were fed normal (0.3%), high (3%) or low (0...