Searchable abstracts of presentations at key conferences in endocrinology

ea0005p223 | Steroids | BES2003

Excretion of the urinary metabolite of deoxycortisol is heritable and influenced by polymorphic variation at the CYP11B2 (aldosterone synthase) locus

Myosi B , Keavney B , Watkins H , Davies E , Ingram M , Fraser R , Connell J

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 ...

ea0005p229 | Steroids | BES2003

Regulation of aldosterone synthase (CYP11B2) gene expression in the rat adrenal gland and central nervous system by sodium and angiotensin II

Ye P , Kenyon C , MacKenzie S , Fraser R , Connell J , Davies E

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...

ea0005p233 | Steroids | BES2003

In vitro synthesis of 18-hydroxycortisol (18-OH-F) and 18-oxocortisol (18-oxo-F); clues to their origin in normal human subjects

Shakerdi L , Friel E , Davies E , Connell J , Wallace A , Fraser R

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 ...

ea0005p234 | Steroids | BES2003

Aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) gene expression in the normal and failing rat heart

Millar C , Ye P , Gray G , Wallace A , MacKenzie S , Fraser R , Connell J , Davies E

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...

ea0005p237 | Steroids | BES2003

Cortisol metabolite excretion and 11-hydroxysteroid dehydrogenase type 1 activity are strongly heritable in man

Myosi B , Watkins H , Keavney B , Ingram M , Fraser R , Davies E , Connell J

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 ...

ea0005p239 | Steroids | BES2003

Effect of dietary sodium manipulation on aldosterone synthase (CYP11B2) gene expression in the rat cardiovascular system

Ye P , Kenyon C , MacKenzie S , Fraser R , Connell J , Davies E

Aldosterone synthase catalyses the synthesis of the mineralocorticoid aldosterone in the adrenal zona glomerulosa and is encoded by the CYP11B2 gene. Recent studies have shown that CYP11B2 is also expressed in the cardiovascular system. CYP11B2 expression in the adrenal gland is regulated by the renin-angiotensin system and potassium. However, little is known about its expression in other tissues. In this study, we have quantitated CYP11B2 expression in the cardiovascular syst...

ea0004p98 | Bone | SFE2002

EFFECT OF ALTERED PTH SENSITIVITY ON BASELINE BONE MINERAL DENSITY IN PATIENTS WITH UNTREATED ADULT GROWTH HORMONE DEFICIENCY

White H , Ahmad A , Peter R , Syed A , Chandran S , Durham B , Fraser W , Vora J

BACKGROUND: Untreated Adult Growth Hormone Deficiency (AGHD) is associated with reduced bone mineral density (BMD). PTH plays an important role in bone metabolism and reports suggest that bone and renal target cell insensitivity to PTH may contribute to changes in bone turnover in AGHD.OBJECTIVES: To determine the difference in PTH and phosphocalcium metabolism in untreated AGHD patients who have normal and reduced BMD.METHODS: 13 ...

ea0004p99 | Bone | SFE2002

GENDER VARIATION IN PTH SENSITIVITY FOLLOWING GROWTH HORMONE REPLACEMENT IN ADULT GROWTH HORMONE-DEFICIENT PATIENTS

White H , Ahmad A , Chandran S , Clewes A , Thomas J , Durham B , Vora J , Fraser W

BACKGROUND: Adult growth hormone deficiency (AGHD) is associated with osteoporosis. Growth Hormone replacement (GHR) results in increased bone mineral density (BMD), with greater benefit derived in men. PTH plays an important role in bone metabolism and reports suggest that bone and renal insensitivity to PTH may contribute to changes in bone turnover in AGHD.OBJECTIVES: To determine the gender difference in PTH, phosphocalcium metabolism and bone turnov...

ea0003p163 | Growth and Development | BES2002

Gender variation in leptin circadian rhythm and pulsatility in adult growth hormone deficiency; effects of growth hormone replacement

White H , Ahmad A , Guzder R , Wallace A , Syed A , Thomas J , Fraser W , Vora J

BACKGROUND: Healthy and Adult Growth Hormone Deficient (AGHD) women exhibit elevated leptin concentrations compared with men. AGHD is characterised by obesity and associated with increased leptin concentration and decreased leptin pulsatility, however the gender variation in rhythm and pulse parameters is yet to be defined. Following growth hormone replacement (GHR), leptin concentration decreases and pulsatility increases preceding a reduction in body fat mass (BFM).<p cl...

ea0003p272 | Steroids | BES2002

Quantification of aldosterone synthase (CYP11B2 ) gene expression in the adrenal gland and central nervous system following dietary sodium manipulation

Ye P , Kenyon C , Mackenzie S , Fraser R , Connell J , Davies E

Objectives: Aldosterone synthase catalyses the synthesis of aldosterone in the adrenal zona glomerulosa and is encoded by the CYP11B2 gene. Recent studies have shown that the CYP11B2 gene is also expressed in the rat central nervous system (CNS), particularly the cerebellum and hippocampus, suggesting local corticosteroid production. The renin-angiotensin system regulates the expression of the CYP11B2 gene in the adrenal cortex. However, little is k...