Endocrine Abstracts

Variation in the human glucocorticoid receptor (GR) gene associates with relative glucocorticoid resistance, hypertension and increased cardiovascular disease risk. Mice heterozygous for a null GR mutation (GR+/−) are also glucocorticoid resistant with raised circulating glucocorticoid levels and elevated blood pressure in adulthood. We have characterised the cardiac phenotype of these mice throughout development and investigated their response to cardiovascul...

2–3% of the UK population are prescribed glucocorticoid (GC) therapy and their adverse effects contribute to a significant health burden. Suppression of endogenous GC secretion is a recognized complication of therapy, but the magnitude of the problem, together with its clinical consequences have not been determined. We conducted a retrospective study across all specialties in a large secondary–tertiary care center identifying 2782 patients who underwent 3666 250 &#95...

Background: Training is adolescent health and transition is lacking in medical education. Clinicians working in diabetes and endocrinology across paediatric and adult services need to have the skills to work effectively with this age group. Our aim was to identify the current state of training and to ascertain training needs in trainees.Methods: A questionnaire was developed based on existing questionnaires. Using trainee representatives all paediatric a...

Chronically elevated glucocorticoid (GC) levels alter cognition and increase cardio-metabolic disease risk. Negative feedback suppression of the hypothalamic–pituitary–adrenal (HPA) axis, including at the hippocampus, maintains low/basal circulating GC levels. Intracellular GC can be increased, without alteration in circulating levels, by the activity of 11β-hydroxysteroid dehydrogenase type1 (11β-HSD1). In some tissues, 11β-HSD1 expression is increase...

Background and aims: Bile acids are conserved through enterohepatic circulation, a glucocorticoid-modulated process. 11β-Hydroxysteroid dehydrogenase type-1 (11β-HSD1) converts cortisone/11-dehydrocortisone to cortisol/corticosterone, thus increasing intracellular glucocorticoid levels. 11β-HSD1 also metabolises 7-oxo-lithocholic acid, a bile acid. 11β-HSD1 is highly expressed in the liver and may alter bile acid transport through regeneration of active glu...

Chronic inflammatory disease is often accompanied by angiogenesis and fibrosis. Glucocorticoids (GCs) exert anti-inflammatory and anti-angiogenic effects, in which macrophages are a major target. Local endogenous GC action is controlled by 11β-hydroxysteroid dehydrogenase (11β-HSD), with the type 1 isozyme, 11β-HSD1 converting inactive GCs into active forms. Mice deficient in 11β-HSD1 have a phenotype consistent with reduced glucocorticoid action, including...

Variation in the glucocorticoid receptor (GR) gene associates with relative glucocorticoid resistance, hypertension and increased cardiovascular disease risk in humans. To investigate the contribution of cardiac GR to this phenotype we have characterised adult male mice with cardiomyocyte and vascular smooth muscle deletion of GR (SMGRKO) and have found left ventricular function to be impaired.SMGRKO mice, generated by crossing GR ‘floxed’ mice...

Glucocorticoid signalling is essential for cardiac maturation late gestation. In mice, global glucocorticoid receptor deficiency (GR−/−) severely impairs cardiac function and ultrastructure at embryonic day (E) 17.5. To dissect direct effects of GR deficiency in the heart from effects on other systems, Sm22α-Cre mice were crossed with ‘floxed’ GR mice to generate SMGRKO mice with disrupted GR signalling in cardiomyocytes and vascular smoot...

11β-Hydroxysteroid dehydrogenase type one (11β-HSD1) converts inert glucocorticoids to active forms, amplifying intracellular glucocorticoid action. 11β-HSD1 also catalyses the reduction of seven-ketocholesterol (7KC) to 7β-hydroxycholesterol (7βHC). 7KC may inhibit cholesterol biosynthesis (Brown et al. 2002). Alteration of cholesterol homeostasis is a major atherosclerotic risk factor. 11β-HSD1 deficiency/inhibition is atheroprotective ...

Background and aims: Bile acids regulate cholesterol metabolism and the digestive system. They are conserved through enterohepatic circulation, a glucocorticoid-modulated process. We investigated whether the regeneration of active glucocorticoid by 11β-hydroxysteroid dehydrogenase type one (11β-HSD1) affects bile acid release and enterohepatic transport after re-feeding.Methods: Bile acid turnover was assessed in global (Hsd11b11<...