Endocrine Abstracts

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...

Although hydrocortisone is the standard replacement therapy for primary or secondary adrenal insufficiency (AI), there are limited data on dosage requirements and the value of salivary monitoring in this patient group. We assessed inter-individual variability in cortisol metabolism and relationships between plasma and salivary cortisol profiles in 27 patients. Ten (3 male) patients had primary AI and 17 (8 male) secondary AI. Salivary and plasma cortisol levels were measured a...

We have shown that linked polymorphisms in the aldosterone synthase gene (CYP11B2) are associated with hypertension and altered aldosterone production. However, the most consistent intermediate phenotype associated with this genetic variation is increased plasma 11-deoxycortisol (S) and urinary excretion of its metabolite, tetrahydrodeoxycortisol (THS); this is paradoxical as S is a substrate for the enzyme 11beta-hydroxylase, encoded by the neighbouring gene, CYP11B1. However...

Background and Hypothesis:- A common NOS3 Single nucleotide polymorphisms (SNP) (894 G/T) which encodes a Glu298Asp amino acid substitution in endothelial NO synthase has been associated with cardiovascular disorders in which NO bioactivity is impaired. The gene coding for p22phox, a critical component of the NADH/NAD(P)H oxidase enzyme system, a major source of vascular SO, is CYBA. Among the allelic polymorphisms reported in CYBA is C242T, associated wit...

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 ...

Aldosterone synthase catalyses the synthesis of aldosterone in the adrenal cortex and is encoded by the CYP11B2 gene. Recent studies have shown that CYP11B2 is also expressed in the central nervous system (CNS) but little is known about its regulation. In this study, we have quantitated CYP11B2 expression in the CNS following dietary manipulation of sodium and infusion of angiotensin II.In study 1, 3 groups of male WKY rats (n=6) were fed normal (0.3%), high (3%) or low (0...

INTRODUCTIONThe plasma concentrations and urinary excretion rates of 18-OH-F and 18-oxo-F are high in Conn's syndrome and glucocorticoid suppressible hyperaldosteronism, reputedly because aldosterone synthase (AS) has abnormal access to cortisol (F). However, both compounds are also excreted in normal subjects. Two enzymes, 11beta-hydroxylase (11OH) and AS, located in the zona fasiculata (ZF) and zona glomerulosa (ZG) respectively, are capable of 18-hydroxylation but only ...

Aldosterone synthase and 11beta-hydroxylase catalyse the final steps of glucocorticoid (corticosterone) and mineralocorticoid (aldosterone) production in the rat adrenal cortex. They are encoded by the CYP11B2 and CYP11B2 genes respectively. Recent studies have shown that CYP11B1 and CYP11B2 are also expressed in the brain, the vascular system and the heart where it has been suggested that aldosterone influences cardiac function and plays a role in cardiac fibrosis. However, i...