Endocrine Abstracts

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. ...

Inactivating mutations of the POMC gene in humans and mice result in a complex phenotype of hyperphagia, obesity and glucocorticoid (GC) deficiency, but without many features of metabolic syndrome. We have previously shown that replacement of GC in Pomc−/− mice exacerbates their hyperphagia, increases fat mass and elevates plasma leptin and insulin. We have now examined key determinants of glucocorticoid action, including glucocorticoid receptor (...

The major glucocorticoids (cortisol in man and corticosterone in the rat) play an important role in obesity and its attendant hypertension. However, there is no consistent evidence of glucocorticoid excess in simple obesity, suggesting that its role in the regulation of adipose tissue mass results from a more complex mechanism than adrenal hypersecretion of glucocorticoid. Glucocorticoid biosynthesis is not limited to the adrenal cortex; mRNA and enzymatic activity of 11β...

Obesity/Metabolic syndrome (insulin resistance, hypertension, cardiovascular disease) has reached epidemic levels in western societies. Aberrantly elevated glucocorticoid amplification by intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) within adipose tissue might explain the striking similarities between idiopathic obesity/metabolic syndrome and Cushing’s syndrome, causes by plasma GC excess. A major contributor to obesity/metabol...

WNK1 (With-No-K, lysine) and WNK4 are serine/threonine kinases, mutated in Gordon syndrome (Pseudohypoaldosteronism Type II), a dominant, hypertensive, hyperkalaemic disorder; implicating this novel WNK pathway in normal regulation of blood pressure (BP) and electrolyte balance. Previous Xenopus oocyte work implicates WNK4 in regulation of K+ secretion via ROMK (renal outer medullary K+ channel) and Cl- transport pathways both paracellularly via tight junctions (claudin...

Adrenal steroids and alterations in steroid metabolism are important factors in the development of obesity in Zucker rats. One might predict, therefore, that the function of the adrenal gland differs between lean and obese Zucker animals. Accordingly, we investigated adrenal gland morphology and function and have considered not only glucocorticoids and HPA activity but also the renin-angiotensin-aldosterone system. Plasma samples and adrenal glands were obtained from young 12 ...

Bile acids inhibit glucocorticoid and mineralocorticoid metabolism. However bile acids may also influence hormone action by modulating steroidogenesis in the adrenal gland. In rodents adrenal cholesterol supply for steroidogenesis is derived from circulating HDL through the actions of scavenger receptor SR-B1. Since hepatic SR-B1 expression is known to be regulated by bile acids, we have investigated whether adrenal SR-B1 is similarly affected and, if so, whether adrenal lipid...

Glucocorticoids mediate the stress response, regulated via the hypothalamic–pituitary–adrenal (HPA) axis. The HPA axis is down-regulated and its responsiveness to stress is impaired in cholestasis. The mechanisms are unknown, but may involve reduced glucocorticoid clearance. Hepatic 5beta-reductase is involved in glucocorticoid inactivation and bile acid biosynthesis. We showed previously that bile acids are potent competitive inhibitors and transcriptional regulator...