Endocrine Abstracts

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...

Glucocorticoids (GC), such as prednisolone, are widely prescribed for their anti-inflammatory and immunosuppressive properties. However, they have significant side-effects including insulin resistance and hepatic steatosis. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts 11-dehydrocorticosterone (11DHC) to active corticosterone (CORT) and thus amplifies local GC action. We hypothesise that enhanced local GC regeneration of exogenously administered GCs by ...

Maternal programming increases the risk of alterations in the offspring’s HPA axis. Previously we showed that maternal undernutrition in sheep induces epigenetic changes in the glucocorticoid receptors (GR) within hypothalamic energy balance pathways, without affecting HPA axis GR. However, these studies focussed on fetal tissues1. Here, we investigated whether GR is epigenetically altered in the HPA axis of adult offspring to determine the status of the pathwa...

Epidemiological studies have identified the intrauterine environment as a major contributor to increased rates of metabolic disease in adults, but the underlying mechanisms are poorly understood. Intrahepatic cholestasis of pregnancy (ICP) is a common liver disease of pregnancy that affects 0.5–2% pregnant women and is characterised by increased bile acid (BA) levels in the maternal serum. The influence of ICP on the metabolic health of offspring is unknown.<p class="...

Obesity is a growing global epidemic and current medical therapies have proven inadequate. Endogenous satiety hormones provide an attractive target for the development of drugs which aim to cause effective weight loss with minimal side effects. Two related peptide hormones, glucagon and glucagon-like peptide 1 (GLP-1), are the subject of this investigation. Both have been found to reduce appetite and cause weight loss. Additionally, glucagon increases energy expenditure. It is...

5α-Reductase 1 (5aR1) catalyses A-ring reduction of glucocorticoids and androgens, predominantly in liver and modulates steroid hormone action. We previously demonstrated transgenic disruption of 5aR1 predisposes mice to developing fatty liver. Here we tested whether 5aR1 disruption increases susceptibility to the development of liver injury, using the carbon tetrachloride induced liver fibrosis model.Male 5aR1−/− (KO) mice and wild-type...

Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder characterized by lifelong elevation of serum calcium concentrations with inappropriately low urinary calcium excretion. Three types referred to as FHH1, FHH2 and FHH3 and located on chromosomes 3q21.1, 19p and 19q13.3, respectively, have been reported. FHH1, caused by loss-of-function mutations of the calcium-sensing receptor (CaSR), accounts for >65% of FHH patients. To identify the gen...

Bone loss in anorexia nervosa and following bariatric surgery is associated with an elevated circulating concentration of the gastrointestinal anorexigenic hormone peptide YY (PYY), which acts principally via the Y1R and Y2R receptors. Selective deletion of Y1R in osteoblasts or Y2R in the hypothalamus results in high bone mass, but deletion of PYY has resulted in conflicting skeletal phenotypes leading to uncertainty regarding its role in the regulation of bone mass. We hypot...