Endocrine Abstracts

The synthesis and metabolism of bile acids and steroid hormones are conflicted at several levels. We investigated potential interactions using a feeding paradigm to stimulate bile acid secretion and salivary steroid measurements to monitor post-prandial changes.The study followed a randomised cross over design; both cortisol and cortisone were measured by specific ELISAs to assess effects on 11 beta-hydroxysteroid dehydrogenase activity (11βHSD). At...

In addition to their essential role in fetal lung development, glucocorticoids promote late-gestation maturation of the fetal heart as shown by severe functional impairment, structural disorganisation and transcriptome immaturity in fetal hearts of glucocorticoid receptor-deficient (GR-/-) mice. Here we use primary fetal mouse cardiomyocytes (E16-E17.5) to investigate whether these effects of glucocorticoids result from direct actions of GR and whether they are independent of ...

Background and aims: Previously we showed that the bioactive liquorice constituent glycyrrhetinic acid (GA) inhibits not only 11β-hydroxysteroid dehydrogenase enzymes but also the sulphation of corticosteroids by the enzyme sulphotransferase 2A1 (SULT2A1). Since pregnenolone, 17α-hydroxy-pregnenolone, deoxycorticosterone (DOC) and dehydroepiandrosterone (DHEA) are all prime substrates for SULT2A1, GA could have important effects in directing pathways of glucocorticoi...

Liquorice root has been used medicinally for many years to treat dry cough, asthma, hunger, thirst, sterility of women, fever, digestive problems and pathologies of organs such as lungs, stomach, intestines and kidney. Glycyrrhetinic acid (one of the active constituents in liquorice) has diverse in vitro effects as an inhibitor of 11β hydroxysteroid dehydrogenase (11HSD), 5α reductase and hormone receptor binding. The aim of this study is to investigate the ef...

Increased 11β hydroxysteroid dehydrogenase type 1 (11βHSD1) activity is implicated in the development of the metabolic syndrome. Identifying natural compounds that influence 11βHSD1 activity could lead to novel methods of treating obesity, cardiovascular disease and diabetes. In the present study, we tested the effect of green coffee bean extract (GCBE), rich in chlorogenic acid (CGA), in human volunteers and of CGA in mice on blood pressure (BP), lipid and gluc...

Deoxycorticosterone (DOC: a weak mineralocorticoid) is the precursor to corticosterone (B: the major glucocorticoid in rodents) and aldosterone. Cyp11b1 encodes 11β-hydroxylase which catalyses the conversion of DOC to B in rodents. The aim of this study is to develop sensitive and specific ELISA methods to estimate urinary DOC and B levels in mice. Antibodies against DOC and B were raised in rabbits by our laboratories as previously described and HRP-Goat anti-Rabbit IgG ...

The majority of immunoassays used to measure aldosterone (most potent mineralocorticoid) levels are still based on radio-iodinated tracer, lack sensitivity and specificity and there is a definite need for their improvement. The aim of this project is to develop a highly sensitive and specific ELISA method for urinary aldosterone estimation in samples obtained from wild type and cyp11b1 knockout mice. Antibodies against aldosterone were raised in sheep as previously described. ...

The rate limiting steps of hepatic glucocorticoid clearance are via A-ring reduction by 5α- and 5β-reductases. Our recent in vitro studies suggested that products of 5α-reduction (eg 5α-tetrahydrocorticosterone) can activate glucocorticoid receptors and hence may contribute to glucocorticoid action in liver. Here we compared the effects of administering 5α-tetrahydrocorticosterone (5αTHB) in vivo with those of corticosterone (B)....

We investigated ACTH-induced hypertension in mice by studying renal function in vivo and by analysing renal gene expression by microarray and RT PCR methods. During two weeks sc infusion with Synacthen, mean blood pressure in adult male mice increased (89±5 vs 110±2 mmHg), and plasma corticosterone, adrenal weights and drinking rate increased by 5, 2 and 2.5-fold respectively (P<0.01); renal mass was unaffected. Greater mineralocorticoid activity wa...

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...