Endocrine Abstracts

GH replacement (GHR) has resulted in a significant improvement in quality of life for many adults with GH deficiency. Many of these patients are previously irradiated survivors of malignancy, and as such are at high risk of recurrent (RN) or secondary neoplasms (SN). There is a particularly strong association between CNS irradiation and subsequent development of meningiomas, which are known to express GH receptors. There is uncertainty as to whether GHR increases the risk of d...

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, ...

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...

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...