Endocrine Abstracts

Salt-sensitive hypertension is a major risk factor for cardiovascular morbidity. Humans and mice with glucocorticoid receptor haploinsufficiency (GR+/−) are hypertensive, which in mice reflects activation of the renin-angiotensin-aldosterone system. Furthermore, glucocorticoid receptor (GR) gene polymorphisms associate with increased cardiovascular disease risk. Here we investigated the effect of dietary salt intake on blood pressure, heart and kidney in GR+/− mice...

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates glucocorticoids in intact cells, converting inert cortisone into active cortisol. We have previously shown attenuated atherosclerosis development, reduced plasma monocyte chemoattractant protein-1 (MCP-1) and reduced macrophage/T cell infiltration within atherosclerotic lesions in 11β-HSD1−/−×ApoE−/− double knock-out (DKO) mice fed western diet (WD)....

High plasma levels of glucocorticoids cause metabolic disease (central obesity, hypertension, diabetes) and increase risk of cardiovascular disease. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates glucocorticoids in intact cells, converting inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone in rodents). Recent work has shown the pathological importance of elevated adipose tissue 11β-HSD1 expression in develo...

Aim: Population studies have shown that basal calcitonin concentrations are below 10 ng/l in the normal population. Ten nanograms per liter is used as a diagnostic cut-off by most laboratories and patients with levels higher than this are offered a pentagastrin stimulation test to exclude medullary thyroid carcinoma. However, these guidelines were adopted from studies that used the Cisbio Immunoradiometric assay for measuring calcitonin. Most laboratories have now moved to che...

Obesity, particularly abdominal (visceral) obesity, is a major risk factor for development of the metabolic syndrome. Human and animal studies have shown elevated intra-adipose glucocorticoid-action in obesity and suggest that increased glucocorticoid receptor (GR) density may be an important determinant of visceral adiposity. We have tested this hypothesis in transgenic (Tg) mice in which adipose GR levels have been increased or decreased, by expression of “sense” o...

Background/objective: We have shown that expression of maternal serum human chorionic gonadotrophin (hCG) oligossacharides in uncomplicated pregnancy differs from that seen in pregnancy complicated by maternal type1 diabetes mellitus. Whether this observed oligosaccharide heterogeneity in type1 diabetes is specific to hCG or represents a more general phenomenon amongst placental oligosaccharides is not known. The oligosaccharide distribution in placentas from pregnancies compl...

Although the anti-inflammatory effects of exogenous glucocorticoids (GC) upon inflammation are well recognized, the contribution of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), an amplifier of GC action in vivo, in modulating endogenous GC action during inflammation is unknown. Mouse models of arthritis and lung inflammation were used to explore the role of 11β-HSD1 in acute and chronic inflammation. Arthritis was induced in 11β-HSD1−/&#...

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 (...

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...

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...