Endocrine Abstracts

The value of mentoring by an experienced, usually older colleague, is widely acknowledged, but just as important is the value of sharing experiences, knowledge and support within a peer group. Peer-to-peer collaboration, or peer mentoring, provides opportunities for networking, friendship, education and career development and advice. Formal groupings and networks often exist locally in the form of student or postdoc societies. The Young Endocrinologists of the Society for Endo...

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...

Background: Chronically elevated brain glucocorticoid (GC) levels impair cognition. In rodents, raised GC levels prior to lipopolyaccharide (LPS) administration potentiate neuroinflammation although GC suppresses neuroinflammation if administered after LPS. 11β-hydroxysteroid dehydrogenase-1 (11β-HSD1) activity can increase intracellular GC levels, including in the brain, without alteration in circulating levels. 11β-HSD1 deficiency/inhibition protects against a...

In addition to their essential role in fetal lung development, glucocorticoids promote late-gestation maturation of the fetal heart as shown by severe functional impairment, structural disorganisation and transcriptome immaturity in fetal hearts of glucocorticoid receptor-deficient (GR-/-) mice. Here we use primary fetal mouse cardiomyocytes (E16-E17.5) to investigate whether these effects of glucocorticoids result from direct actions of GR and whether they are independent of ...

The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), regenerates active glucocorticoids (cortisol, corticosterone) from inert substrates (cortisone, 11-dehydrocorticosterone) and has been implicated in the pathogenesis of the metabolic syndrome. 11β-HSD1 expression is increased in adipose tissue and decreased in liver in human and rodent obesity. Paradoxically, in chronically high fat-fed mice 11β-HSD1 is down-regulated in adipose tissue. Transcri...

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...