Endocrine Abstracts

Increased intake of sodium is postulated to be controlled by aldosterone-sensitive cells in a select region of the adult mouse brain, the nucleus of the solitary tract (NTS). These cells express the enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD2) which inactivates glucocorticoids, allowing selective activation of mineralocorticoid receptors by aldosterone. However in the developing brain, HSD2 is widely expressed to protect against adverse glucocorticoid action, whi...

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 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...

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...