Endocrine Abstracts

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 ...

Liquorice root has been used medicinally for many years to treat dry cough, asthma, hunger, thirst, sterility of women, fever, digestive problems and pathologies of organs such as lungs, stomach, intestines and kidney. Glycyrrhetinic acid (one of the active constituents in liquorice) has diverse in vitro effects as an inhibitor of 11β hydroxysteroid dehydrogenase (11HSD), 5α reductase and hormone receptor binding. The aim of this study is to investigate the ef...

The rate limiting steps of hepatic glucocorticoid clearance are via A-ring reduction by 5α- and 5β-reductases. Our recent in vitro studies suggested that products of 5α-reduction (eg 5α-tetrahydrocorticosterone) can activate glucocorticoid receptors and hence may contribute to glucocorticoid action in liver. Here we compared the effects of administering 5α-tetrahydrocorticosterone (5αTHB) in vivo with those of corticosterone (B)....

Introduction: Humans with glucocorticoid receptor (GR) deficiency and global heterozygous GR knockout (GR+/−) show compensatory activation of the hypothalamic-pituitary-adrenal axis, resulting in salt-sensitive hypertension due to increased mineralocorticoid activity. Previous studies suggest renal mechanisms, including changes in cell proliferation, gene expression and electrolyte transport, may contribute to this phenotype but underlying adaptive adrenal responses have...

Mice with congenital adrenal hyperplasia due to a null mutation of cyp11b1, the gene encoding the steroidogenic enzyme 11β-hydroxylase, have low glucocorticoid levels, reduced adiposity and increased liver weight. It is notable that null mice are also glucose intolerant. Here, we have investigated these phenotypes in more detail. Plasma corticosterone levels were less responsive to restraint stress and cholesterol and triglyceride levels were not significantly different i...

Glycyrrhetinic acid (GA) has diverse in vitro effects as an inhibitor of 11beta hydroxysteroid dehydrogenase (11HSD), 5alpha reductase and hormone receptor binding. However, in vivo GA studies have focussed on the hypertensive effects associated with the syndrome of apparent mineralocorticoid excess (SAME) in which 11HSD inhibition allows glucocorticoid hormones to bind inappropriately to MR and subsequent decreased aldosterone synthesis. Here we consider whether...