Searchable abstracts of presentations at key conferences in endocrinology

ea0011p762 | Steroids | ECE2006

Differential regulation of Cyp4A isoforms in mouse kidney during the development of mineralocorticoid, salt-sensetive induced hypertension

Marshall E , Roy D , Mullins J , Kenyon C , Brown R

Arachidonic acid (AA) metabolites derived from cytochrome P450 enzymes regulate vascular tone and renal tubular function. The cytochrome P450 4A (Cyp4A) enzymes are responsible for the synthesis of 20- hydroxyeicosatetraenoic (20-HETE), the most abundantly produced AA Cyp P450 metabolite in the kidney. Cyp4a expression and the production of 20-HETE, have been implicated in the development of hypertension. Here we have investigated the expression of various renal isoforms of Cy...

ea0009p138 | Steroids | BES2005

WNK kinases; a novel pathway regulating electrolyte balance and blood pressure, which is mutated in Pseudohypoaldosteronism type II

O'Reilly M , Marshall E , Mittal M , Kenyon C , Brown R

WNK1 and WNK4 are serine/threonine kinases, With-No-K (lysine) residue at a key catalytic position within the active site. Mutations in either cause Pseudohypoaldosteronism type II (Gordon syndrome), an autosomal dominant, hypertensive, hyperkalaemic disorder, especially responsive to thiazide diuretics (first line treatment for essential hypertension). This novel WNK pathway is implicated in normal regulation of blood pressure (BP) and distal nephron Na+/K+</s...

ea0005oc5 | Reproduction and Development | BES2003

Angiotensinogen; the key to programming female hypertension?

O'Regan D , Kenyon C , Seckl J , Holmes M

Adverse events in utero permanently alter the structure and physiology of adult offspring, a phenomenon termed 'foetal programming'. In particular, low birth-weight is associated with an increased risk of adulthood hypertension. Glucocorticoid (GC) administration during pregnancy reduces offspring birth-weight and GCs directly elevate blood pressure (BP) in both humans and rodents. Circulating and local renin-angiotensin-aldosterone (RAAS) system(s) may be involved in programm...

ea0019oc2 | Young Endocrinologist prize session | SFEBES2009

Anti-inflammatory effects of 5 alpha-reduced glucocorticoids in vitro and in vivo

Yang C , Rossi A , Duffin R , Livingstone D , Kenyon C , Walker B , Andrew R

Previously, we have shown that 5α-tetrahydrocorticosterone (5αTHB), the reduced metabolite of corticosterone (B, the main glucocorticoid in rodents), binds to the glucocorticoid receptor, suppresses the HPA axis but has weak in vivo effects on adipose tissue and liver metabolism. Here we have compared the anti-inflammatory effects of B and 5αTHB in three in vitro and in vivo experiments. Cytokine release was measured by cytometric bead array...

ea0019p143 | Diabetes, Metabolism and Cardiovascular | SFEBES2009

Increased mineralocorticoid activity in obese Zucker rats is independent of the renin–angiotensin system and hepatic steroid metabolism.

Kenyon C , Livingstone D , Ingram M , Al-Dujaili E , Rutter A , Fraser R , Andrew R

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 ...

ea0009p139 | Steroids | BES2005

Profiling aldosterone and salt responsive pathways in an inducible hypertensive mouse model

Marshall E , Forster T , Dickenson P , Roy D , Mullins J , Kenyon C , Brown R

The kidney plays a dominant role in long-term blood pressure (BP) control and electrolyte homeostasis but aldosterone (aldo) responsive molecular pathways in the kidney involved in regulating BP remain poorly understood despite identification of several participant genes. Many human single gene disorders affecting BP have been faithfully reproduced in mice by targeting the corresponding genes. Thus mouse is an excellent model to study molecular pathways underlying hypertension...

ea0007p206 | Steroids | BES2004

Regulation of 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) gene expression in the rat adrenal gland and central nervous system by ACTH and dexamethasone

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

11Beta-Hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) catalyse the synthesis of corticosterone and aldosterone respectively in the rat adrenal cortex. Recent studies have shown that CYP11B1 and CYP11B2 are also expressed in the central nervous system (CNS) but little is known about their regulation. In this study, we have quantified CYP11B1 and CYP11B2 gene expression in the CNS following treatment with ACTH and dexamethasone.Three groups of ma...

ea0007p209 | Steroids | BES2004

The effect of adrenalectomy on 11beta-hydroxylase(CYP11B1) and aldosterone synthase (CYP11B2) gene expression in the hippocampus

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

11Beta-Hydroxylase and aldosterone synthase catalyse the synthesis of corticosterone and aldosterone in the rat adrenal cortex and are encoded by the CYP11B1 and CYP11B2 genes respectively. These genes are also expressed in distinct regions of the CNS and cardiovascular system where they may play a key role in behavioural response and blood pressure homeostasis. However, it is unclear whether this extra-adrenal expression is regulated by, or contributes to, circulating levels ...

ea0007p225 | Steroids | BES2004

Gene expression responses induced in kidney by aldosterone excess and salt

Marshall E , Dickenson P , Forster T , Roy D , Kenyon C , Brown R

Renal sodium handling and responses to aldosterone (aldo) are conserved across species and intrinsic to the dominant role of the kidney in long-term blood pressure (BP) control. Molecular pathways involved in hypertensive responses to aldo and escape from these remain largely unclear despite identification of several participant genes. We have characterized renal gene expression changes in mice, receiving aldo and/or dietary salt excess, using microarray analysis and concurren...

ea0005oc21 | Obesity and Diabetes | BES2003

5alpha-Reduced glucocorticoid metabolites: Novel endogenous activators of glucocorticoid receptors(GR)

McInnes K , Livingstone D , Kenyon C , Chapman K , Walker B , Andrew R

Metabolism of glucocorticoids to dihydro and tetrahydro derivatives via hepatic 5alpha- and 5beta-reductases has been assumed to be a pathway of irreversible inactivation of glucocorticoids. However, 5alpha-reduced metabolites of other steroids (testosterone, aldosterone) have significant affinity for the parent hormone receptor. We have investigated whether 5alpha-reduced metabolites of corticosterone (B) are GR agonists.In hepatocytes from male lean Zucker rats (n=6) com...