Endocrine Abstracts

Hypertension in obese Zucker rats is associated with raised plasma aldosterone, suppressed renin and increased hypothalamo–pituitary–adrenal activity. We investigated the possible causes and consequences of these associations by comparing adrenal gene expression and urinary electrolyte and steroid excretion patterns in lean and obese rats. Groups (n=11) of adult male lean and obese Zucker rats were held in metabolism cages for 7 days. Urine collected over the ...

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...

There is considerable evidence to indicate that the hypothalamic-pituitary-adrenal axis is activated in obesity and that glucocorticoids may have a stimulatory effect on adipocyte leptin production. However, the precise interactions between glucocorticoids and leptin are complex and remain poorly understood. To investigate whether the glucocorticoid/leptin interaction is affected by genetic factors, we investigated the heritability of BMI, leptin and glucocorticoid metabolite ...

18-hydroxycortisol (18-OHF) and 18-oxocortisol (18oxo-F) are derivatives of cortisol whose origin and regulation are uncertain. 18-OHF is synthesised by zona fasciculata 11-beta hydroxylase; 18-oxoF can only be produced by zona glomerulosa aldosterone synthase. Levels of both steroids are increased in patients with Primary Aldosteronism. However, the origin of these steroids in normal subjects is not known.8 normal subjects and 6 subjects with primary adrenal failure performed...

Background: The enzymes 11beta-hydroxylase and aldosterone synthase are key control steps in regulation of cortisol and aldosterone synthesis. We have previously reported that polymorphic variation of the gene encoding aldosterone synthase (CYP11B2) is associated with altered efficiency of 11b-hydroxylation of the precursor of cortisol, deoxycortisol. In order to examine this relationship in greater detail, we have studied the pattern of steroid precursor metabolite excretion ...

Background: Cortisol availability to target tissues represents a complex interplay of synthesis, secretion, metabolism and excretion. A number of these processes are regulated by enzymes that are encoded by genes that are key candidates in determining the metabolic and cardiovascular phenotype in man. Measurement of a range of corticosteroid metabolites allows the activity of these enzymes to be inferred. We have studied the pattern of cortisol metabolite excretion in a large ...

Background: A polymorphism within the CYP11B2 gene, characterised by a C/T substitution at position 344, the putative binding site for steroidogenic transcription factor1, has been shown to influence aldosterone excretion rate and blood pressure in essential hypertension.Aims: Assess the effect of contrasting genotype for the SF1 site on urinary and plasma steroid production during dietary manipulation of the renin-angiotensin system and assess the press...

Aldosterone is an important cardiovascular hormone. Around 15 % of hypertensives have alteration in aldosterone regulation, defined by a raised ratio of aldosterone to renin (ARR). Studies of CYP11B2, the aldosterone synthase gene, focus on a single nucleotide polymorphism in the 5'promotor region (-344 C/T). We have shown that the T allele is associated with increased urinary excretion and plasma levels of aldosterone and is more common amongst hypertensives with a raised ARR...

The regulation of aldosterone secretion is altered in essential hypertension: the phenotype of relative aldosterone excess is present in up to 15% of subjects. The gene encoding aldosterone synthase (CYP11B2) offers an obvious candidate to account for this and a polymorphism in its 5′ untranslated region (UTR; −344C/T) is associated with increased frequency of hypertension and higher aldosterone levels. However, this variation is more closely associated with...

Background: Glucorticoids can affect blood pressure in humans, as demonstrated most strikingly in Cushing’s syndrome. We have previously reported that total cortisol metabolite excretion is raised in obese subjects, while other investigations have identified genetically determined changes in glucocorticoid receptor function as contributors to hypertension. Furthermore, in essential hypertension, vasoconstrictor sensitivity to glucocorticoids is increased. Such raised sens...