Endocrine Abstracts

Glucocorticoids synchronise peripheral clocks with the master clock in the suprachiasmatic nucleus of the brain. In humans and mice, abnormal glucocorticoid rhythms induce blood pressure abnormalities accompanied by vascular dysfunction. The mechanisms of this remain unclear. We hypothesise that excessive activation of the glucocorticoid receptor (GR) disrupts circadian clock signalling, altering vascular function and inducing non-dipping blood pressure. We characterise the va...

In neonates, cardiomyocytes exit the cell cycle thus establishing cardiomyocyte number for life. Further growth is through hypertrophy. Factors that advance the timing of the switch from hyperplastic to hypertrophic growth may increase risk of cardiac disease in adulthood. Early life administration of glucocorticoids is known to increase risk of cardiovascular disease. We hypothesized that dexamethasone, a synthetic glucocorticoid, causes precocious cell cycle exit of neonatal...

Background: During fetal development, the heart switches substrate preference from glucose to fatty acids, such that in the adult heart, 50–70% of ATP is derived from fatty acid oxidation. What triggers this switch is currently unclear. In vivo, the late gestation rise in glucocorticoid levels is essential for structural and functional maturation of the fetal heart. Glucocorticoid treatment of fetal cardiomyocytes induces express...

Background: During fetal development, the heart switches substrate preference from glucose to fatty acids, such that in the adult heart, 50–70% of ATP is derived from fatty acid oxidation. What triggers this switch is currently unclear. In vivo, the late gestation rise in glucocorticoid levels is essential for structural and functional maturation of the fetal heart. Glucocorticoid treatment of fetal cardiomyocytes induces express...

During early life, the majority of cardiomyocytes exit the cell cycle and undergo terminal differentiation, becoming binucleated. This establishes the number of cardiomyocytes for the remainder of the lifetime, with subsequent consequences for cardiac resilience in adulthood. Activation of the glucocorticoid receptor (GR) is important for heart maturation: fetal mice lacking GR in cardiomyocytes (SMGRKO) show structural and functional cardiac immaturity. Young adult male and f...

The late gestation increase in glucocorticoid action promotes the structural and functional maturation of the fetal heart. Metabolic maturation of cardiomyocytes involves a switch from glucose utilization as a fuel source to fatty acid (FA) oxidation. In fetal cardiomyocytes, glucocorticoids induce expression of PGC1a (a master regulator of mitochondrial capacity), lipin1 and KLF15 (genes involved in FA oxidation). We hypothesized that glucocorticoids promote the metabolic swi...

Background: The late gestational surge in glucocorticoids is vital for the maturation of fetal organs in preparation for birth and survival during the neonatal period. Metabolic maturation of cardiomyocytes involves a switch in fuel substrate from glucose utilization to fatty acid (FA) oxidation. In fetal cardiomyocytes, glucocorticoids induce expression of Ppargc1a (encoding PGC1a, a master regulator of mitochondrial capacity). We hypothesized that glucocorticoids pr...