Searchable abstracts of presentations at key conferences in endocrinology

ea0025oc2.3 | Steroids | SFEBES2011

APEX1, a novel, negative regulator of aldosterone synthase activity, differentially binds to a single nucleotide polymorphism in the aldosterone synthase gene and represses transcriptional activity both in vitro and in vivo

McManus Frances , Sands William , Fraser Robert , Davies Eleanor , Connell John

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...

ea0025p275 | Reproduction | SFEBES2011

Male germ cell activity during perinatal reproductive development in the mouse

Jarvis Sheba , Winston Robert , Fraser Scott , Readhead Carol

Dynamic changes in gene expression patterns and cell behaviour are evident throughout embryonic and neonatal germ cell development in the mouse. In the testes, the postnatal period represents a time when the male germline stem cells (GSCs) or, gonocytes migrate to the basement membrane of the seminiferous tubules preparing for a lifetime of spermatogenesis and is an important area of study. Here we use the transgenic mouse that expresses green fluorescent protein under the Oct...

ea0025p290 | Steroids | SFEBES2011

Urinary tetrahydroaldosterone excretion is determined by rising urinary sodium excretion in patients with chronic kidney disease

McQuarrie Emily , Mark Patrick , Fraser Robert , Davies Eleanor , Connell John , Freel E Marie

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...

ea0021p348 | Steroids | SFEBES2009

−344 C/T polymorphism of aldosterone synthase gene (CYP11B2) and cortisol synthesis in heart failure patients

Tsorlalis Ioannis , Fraser Robert , Jackson Colette , Ingram Mary , Holloway Christine , McMurray John , Connell John

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...

ea0021p362 | Steroids | SFEBES2009

MicroRNA expression profiling of non-tumorous adrenal tissue and modulation of 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes by miR-24

Wood Stacy , MacKenzie Scott , Stewart Paul , Fraser Robert , Connell John , Davies Eleanor

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...

ea0013oc19 | Novartis Basic Endocrinology Award | SFEBES2007

Steroidogenic gene transcription in the human hippocampus and cerebellum: a comprehensive survey

MacKenzie Scott , Dewar Deborah , Stewart William , Fraser Robert , Connell John , Davies Eleanor

Previous studies investigating steroidogenic enzymes in the brain have often focused on only a few genes at a time, using animal models or pooled human RNA to investigate their expression. For this study, we obtained RNA from individual archived human brain tissue samples in order to analyse the transcription of twelve genes involved with steroid biosynthesis and metabolism within the cerebellum and hippocampus.We developed realtime RT-PCR assays for twe...

ea0013oc24 | Neuroendocrinology, reproduction and cardiovascular | SFEBES2007

Acute aldosterone responses to ACTH predict both cortisol responses and blood pressure

Reynolds Rebecca , Walker Brian , Phillips David , Syddall Holly , Davies Eleanor , Fraser Robert , Connell John

Background: Aldosterone levels in plasma are reported to be associated with risk of hypertension. Aldosterone secretion from the zona glomerulosa is regulated acutely by the renin/angiotensin system and plasma potassium. The role of ACTH in regulation of aldosterone secretion is disputed.Aim: We have utilised a large population study of middle aged adults to test the extent to which acute aldosterone responses to ACTH are associated with cortisol respons...

ea0013oc30 | Neuroendocrinology, reproduction and cardiovascular | SFEBES2007

Consequences of variation in the CYP11B2 and CYP11B1 genes on hypothalamic-pituitary-adrenal axis activity

Freel E Marie , White Ann , Ingram Mary , Fraser Robert , Davies Eleanor , Connell John

Aldosterone is key in the development of hypertension. We have shown that a SNP (−344T) in the 5’ regulatory region (UTR) of the gene encoding aldosterone synthase (CYP11B2) was associated with aldosterone excess and high blood pressure. However, the most robust phenotype is altered adrenal 11-hydroxylation efficiency (deoxycortisol to cortisol); a step carried out by 11β-hydroxylase, encoded by the adjacent gene, CYP11B1. We proposed that the effects of CYP11B...

ea0034oc3.5 | Steroids | SFEBES2014

Linking GWAS to gene function: CYP17A1 in hypertension

Diver Louise , MacKenzie Scott , McManus Frances , Freel Marie , Friel Elaine , Fraser Robert , Hanley Neil , Connell John , Davies Eleanor

Recent genome-wide association studies (GWAS) implicate the CYP17A1 locus in human blood pressure regulation. This gene is important in steroidogenesis, regulating both glucocorticoid and androgen synthesis through catalysis of 17α-hydroxylation and 17,20 lyase reactions. We hypothesised that functional CYP17A1 polymorphisms linked to those identified by GWAS influence blood pressure levels. We therefore screened the entire CYP17A1 locus by dire...