Endocrine Abstracts

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...

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...

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...

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 ...

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...

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...