Endocrine Abstracts

Up to 15% of unselected patients with hypertension have evidence of inappropriate aldosterone production, identified by a raised ratio of plasma aldosterone to renin (ARR), suggesting that altered regulation of aldosterone synthesis is a key intermediate phenotype in essential hypertension. We previously described an association between the -344C/T 5'UTR polymorphism in the CYP11B2 (aldosterone synthase) gene and hypertension with raised ARR; the same genetic variation associa...

Background: The CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) genes are found in close proximity on human chromosome 8 and are highly polymorphic, enabling the definition of two common haplotypes. Haplotype1 includes the -344T and the Intron2 conversion polymorphisms in CYP11B2 and also the -1889T, -1859G polymorphisms in the regulatory region of CYP11B1. We and others have shown that these associate with increased aldosterone pr...

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...

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...

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...

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 ...

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...

Aldosterone synthase and 11beta-hydroxylase catalyse the final steps of glucocorticoid (corticosterone) and mineralocorticoid (aldosterone) production in the rat adrenal cortex. They are encoded by the CYP11B2 and CYP11B2 genes respectively. Recent studies have shown that CYP11B1 and CYP11B2 are also expressed in the brain, the vascular system and the heart where it has been suggested that aldosterone influences cardiac function and plays a role in cardiac fibrosis. However, i...

Aldosterone synthase catalyses the synthesis of the mineralocorticoid aldosterone in the adrenal zona glomerulosa and is encoded by the CYP11B2 gene. Recent studies have shown that CYP11B2 is also expressed in the cardiovascular system. CYP11B2 expression in the adrenal gland is regulated by the renin-angiotensin system and potassium. However, little is known about its expression in other tissues. In this study, we have quantitated CYP11B2 expression in the cardiovascular syst...

Objectives: Aldosterone synthase catalyses the synthesis of aldosterone in the adrenal zona glomerulosa and is encoded by the CYP11B2 gene. Recent studies have shown that the CYP11B2 gene is also expressed in the rat central nervous system (CNS), particularly the cerebellum and hippocampus, suggesting local corticosteroid production. The renin-angiotensin system regulates the expression of the CYP11B2 gene in the adrenal cortex. However, little is k...