Endocrine Abstracts

Hypertension is one of the most common risk factors for cardiovascular disease and is well known to have a substantial heritable component. The mineralocorticoid aldosterone plays a key role in the regulation of BP and excess production can lead to hypertension. Therefore, much attention has focused on the genes mediating its biosynthesis.The terminal stage of aldosterone production is catalysed by the aldosterone synthase enzyme, encoded by the CYP1...

Hypertension is one of the most common risk factors for cardiovascular disease and is well known to have a substantial heritable component. The mineralocorticoid aldosterone plays a key role in the regulation of BP and excess production can lead to hypertension. Therefore, much attention has focused on the genes mediating its biosynthesis.The terminal stage of aldosterone production is catalysed by the aldosterone synthase enzyme, encoded by the CYP1...

Aldosterone synthesis is heritable; a single nucleotide polymorphism (SNP) in the promoter of the aldosterone synthase gene (position −344, rs1799998) has been associated with an increased plasma aldosterone levels and hypertension. However, deletion of this site has no effect on gene transcription in vitro and therefore the mechanism that links genotype with phenotype is unclear.We identified a polymorphism at position −1651 T/C (rs13...

The aldosterone synthase gene encodes the final step in the production of aldosterone. The aldoststerone synthase gene is polymorphic and variants within the gene and the regulatory region have been associated with hypertension and a phenotype of relatively higher level of aldosterone and its metabolites. However to date; none of the polymorphisms in the regulatory region of CYP11B2 have been shown to alter transcription. Seven novel polymorphisms in the promoter region of CYP...

Hypertension is the most important risk factor in the development of cerebrovascular diseases including vascular cognitive impairment (VCI). Aldosterone is a key regulator of blood pressure, acting via the mineralocorticoid receptor (MR) in the kidney to promote sodium/water reabsorption. Elevated aldosterone, as in primary aldosteronism (PA) is a risk factor for cerebrovascular disease. In addition to its traditional role, the MR is expressed throughout the brain and vasculat...

Introduction: Measurement of microRNA (miRNA) in aldosterone-producing adenoma (APA) tissue from primary aldosteronism (PA) patients show levels of the miR24-1 cluster miRNAs (i.e. miRNAs 24-1, 27b and 23b) are significantly reduced relative to normal adrenal tissue. Our previous studies also show that miRNA-24 directly targets CYP11B2 (aldosterone synthase) gene expression. Circulating miRNAs released into the bloodstream may be diagnostic biomarkers or signalling mo...

Approximately 10% of essential hypertension cases is attributed to primary aldosteronism (PA), where inappropriately high levels of aldosterone are secreted. Almost half of these PA cases result from aldosterone-producing adenoma. microRNAs are single-stranded, short non-coding RNAs that negatively regulate gene expression post-transcriptionally. In a previous study, we showed that microRNAs directly modulate CYP11B2 (aldosterone synthase) gene expression and aldoster...

Many cases of hypertension are associated with inappropriately high levels of aldosterone secretion and it has been proposed that microRNAs play a role in this dysregulation. Previously, we showed that microRNAs expressed within the adrenal cortex significantly repress aldosterone production. Furthermore, stimulation of aldosterone secretion by three different means in the H295R cell line – the most commonly-used in vitro model of the human adrenal cortex – ...

Inappropriately high secretion of aldosterone can lead to hypertension and its various cardiovascular consequences. We previously showed that microRNA (miRNA) plays a significant role in the regulation of aldosterone biosynthesis. In this study we measured miRNA levels in H295R cells, the most commonly-used human adrenocortical cell line, and investigated how these change in response to the stimulation of aldosterone biosynthesis.H295R cells (n=...

The CYP11B1 and CYP11B2 genes encode the enzymes responsible, respectively, for the terminal stages of cortisol and aldosterone biosynthesis, and have been implicated in the development of essential hypertension. Previously, we investigated the role of microRNAs in the regulation of these genes and showed in vitro that levels of the adrenally-expressed microRNA-24 (miR-24) inversely correlate with those of CYP11B1 and CYP11B2 mRNA, ...