Endocrine Abstracts

Congenital imprinting disorders (IDs) are a group of rare conditions affecting growth, metabolism and development caused by aberrant expression of imprinted genes in a parent-of-origin dependent manner. The internationally recognised IDs are Prader Willi Syndrome (PWS), Angelman Syndrome (AS), Beckwith Wiedemann Syndrome (BWS), Silver Russell Syndrome (SRS), Temple Syndrome (TS14), Pseudohypoparathyroidism (PHP), Transient Neonatal Diabetes Mellitus (TNDM) and Kagami-Ogata Syn...

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...

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, ...

The final reaction for cortisol production in the adrenal gland is catalysed by the 11β-hydroxylase enzyme, encoded by the CYP11B1 gene. Variants in this gene have been associated with alterations in cortisol levels, which increase blood pressure. This gene is traditionally thought to consist of 9 exons. However, recent evidence has predicted the existence of at least one alternatively spliced form.The presence of novel CYP11B1 mRN...

Essential hypertension is known to have a large genetic component. Variation in the CYP11B2 gene, which encodes the aldosterone synthase enzyme, is associated with excess aldosterone production and hypertension but the causative mechanism remains elusive. miRNAs are a class of post-transcriptional regulatory molecules, implicated in cardiovascular disease, development and tumourogenesis. They act by targeting the 3′ untranslated region (UTR) of mRNAs, inhibiting t...

Aim: In chronic kidney disease (CKD) elevated aldosterone (Aldo) levels are a poor prognostic indicator, particularly in the context of a high dietary sodium intake, through unclear mechanisms. Blockade of the mineralocorticoid receptor (MR) improves surrogate patient outcomes. We hypothesised that regulation of aldosterone biosynthesis is disordered in CKD and aimed to compare this in a cohort of patients with CKD with subjects with essential hypertension (EH).<p class="a...

Background: Increased levels of cortisol are associated with worse prognosis in heart failure (HF). The final step in cortisol production is catalysed by 11β-hydroxylase encoded by CYP11B1, which is highly homologous with CYP11B2. A common polymorphism in the aldosterone synthase gene (CYP11B2 −344T) is associated with a raised ratio of 11-deoxycortisol/ cortisol (S/F). We examined the relationship between −344C/T polymorphism and corticos...

The CYP11B1 and CYP11B2 genes encode 11β-hydroxylase and aldosterone synthase, which catalyse the production of cortisol and aldosterone, respectively, and have been implicated in the development of hypertension. For this study, we wished to investigate the role of microRNAs (miRNAs), a novel class of post-transcriptional gene regulators. To that end, we generated a profile of human adrenal miRNAs to study, and then investigated the action of one adrenal miR...

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...

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...