Endocrine Abstracts

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...

Aim: We propose that the circulating immune system and adipocyte size plays a role in the development of obesity related co-morbidities independent of body mass index (BMI).Methods: Clinical data and blood samples were collected from patients with severe obesity attending a hospital weight-management clinic and lean healthy controls. Patients were classified into metabolically ‘healthy obese’ or ‘unhealthy obese’ groups, based upon st...

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...

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...

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...

(This poster is based on OC19)...

A common NOS3 polymorphism (the gene which encodes endothelial nitric oxide synthase), a variable number of tandem repeats within Intron 4 has been associated with cardiovascular disorders in which nitric oxide bioactivity is impaired including myocardial infraction. Consistent characteristic changes in the pressure pulse wave shape have been associated with ageing, risk factors for cardiovascular disease and impaired NO bioactivity. Therefore pulse waveform analysis can be ut...

The major glucocorticoids (cortisol in man and corticosterone in the rat) play an important role in obesity and its attendant hypertension. However, there is no consistent evidence of glucocorticoid excess in simple obesity, suggesting that its role in the regulation of adipose tissue mass results from a more complex mechanism than adrenal hypersecretion of glucocorticoid. Glucocorticoid biosynthesis is not limited to the adrenal cortex; mRNA and enzymatic activity of 11β...

Surgery is the most effective way of treating morbid obesity. The laparoscopic gastric bypass (Roux en-Y) is the preferred bariatric surgical procedure performed at our hospital. This combines restriction of intake with a profound sensation of early satiety.Ideally, multi-disciplinary team involvement (including psychological assessment), over a period of at least six months, is a prerequisite for bariatric surgery referral. The more psychotherapeutic wo...

Corticosteroids can be synthesised in tissues other than the adrenal cortex but the contribution of this extra-adrenal corticosteroidogenesis to circulating levels in man is not known. We studied this in a group 10 subjects taking chronic glucocorticoid replacement following bilateral adrenalectomy. In phase 1, they were maintained on cortisol alone (30 mg/day). In phase 2, cortisol was replaced by dexamethasone (2 mg/day) and in phase 3, they received both cortisol and dexame...