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...

Glucocorticoid levels rise dramatically in late gestation in mammals and are essential for organ maturation in preparation for birth. They are widely used clinically to mature the lungs of premature infants and hypomorphic GR mice die neonatally due to severe lung atelectasis. Here, we describe fetal lethality in GR null (GR−/−) mice with 51% loss at E17.5 (P<0.05) that could be due to impaired cardiac development. Histology showed reduced hea...