Endocrine Abstracts

Background: Alström Syndrome (AS) is a rare autosomal recessive disease featuring highly accelerated insulin resistance, fatty liver, diabetes and heart failure among other syndromic features. Heart failure leads to significant early mortality, but is complex and likely multifactorial, with developmental defects, accelerated atherosclerosis, and fibrosis all implicated. These cardiometabolic complications occur in the face of only moderate obesity in many patients. AS is ...

Synthetic glucocorticoids are administered to pregnant women at risk of pre-term delivery to mature organs and improve neonatal survival. We have shown that glucocorticoid action is essential to mature the fetal heart. Here, we tested the hypotheses that antenatal glucocorticoid exposure, prior to the normal increase in glucocorticoid levels, will advance fetal heart maturation and this will depend on cardiovascular glucocorticoid receptor (GR).Male SMGR...

Glucocorticoids are routinely administered to pregnant women at risk of pre-term delivery to mature foetal organs and improve neonatal survival. Previous work in glucocorticoid receptor (GR)-deficient mice showed that GR activation is essential for maturation of the foetal heart. Here, we tested the hypotheses that i) antenatal glucocorticoid exposure, prior to the normal increase in glucocorticoid levels, will advance foetal heart maturation and ii) this would depend on mater...

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...

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...

Specific variations in the human glucocorticoid receptor (GR) gene associate with increased cardiovascular disease risk. GR signalling is essential for cardiac maturation in utero and adult mice with cardiomyocyte and vascular smooth muscle deletion of GR (SMGRKO mice) have cardiac hypertrophy, fibrosis and impaired function. Intriguingly, levels of left ventricle (LV) mRNA encoding the mineralocorticoid receptor (MR), which is pro-fibrotic in heart, rise postnatally ...

Caloric restriction (CR) is a nutritional intervention that reduces the risk of age-related diseases in numerous species, including humans. CR’s metabolic effects, including decreased fat mass and improved insulin sensitivity, play an important role in its broader health benefits, yet many aspects of the CR response remain poorly understood. In particular, sex differences in metabolic function are increasingly well recognised, but the extent and basis of sex differences i...

Glucocorticoids (GCs) protect cardiomyocytes immediately after myocardial infarction (MI), but GCs subsequently regenerated within the heart by 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) are detrimental during infarct repair, with functional outcomes post-MI improved in mice lacking 11βHSD1. Pharmacological 11βHSD1 inhibition (AZD8329 50mg/kg, 11βHSD1i) was compared to standard clinical therapy (SCT) in a translational pig model (female, 11βHSD1...