Endocrine Abstracts

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...

11β-Hydroxysteroid dehydrogenase type one (11β-HSD1) converts inert glucocorticoids to active forms, amplifying intracellular glucocorticoid action. 11β-HSD1 also catalyses the reduction of seven-ketocholesterol (7KC) to 7β-hydroxycholesterol (7βHC). 7KC may inhibit cholesterol biosynthesis (Brown et al. 2002). Alteration of cholesterol homeostasis is a major atherosclerotic risk factor. 11β-HSD1 deficiency/inhibition is atheroprotective ...

Glucocorticoids (GCs) are highly effective anti-inflammatory drugs, however their use is limited by serious side effects. We have previously shown that 5αTHB binds GC receptor (GR) and suppresses inflammation in vitro and in vivo, without affecting metabolism. Here the underlying molecular mechanisms were explored in cell models of ligand-induced GR phosphorylation, nuclear localisation and gene transcription. Data are mean±S.E.M. (th...

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...

Introduction: Heavy menstrual bleeding (HMB) affects over 1 million women in the UK. At menses, progesterone (P4) withdrawal drives inflammation, tissue break-down and repair of the endometrium. Glucocorticoids are mediators of inflammation and angiogenesis. Our previous studies have demonstrated that differential endometrial expression of the glucocorticoid-metabolising enzymes, 11β-HSD-1 and -2, may play a role in HMB. We hypothesise that aberrant lo...

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoids thus amplifying their intracellular actions. 11β-HSD1 deficiency or inhibition, which improve metabolic syndrome and attenuate atherosclerosis in vulnerable rodent strains, is a target for drug development. However, 11β-HSD1 also converts 7-ketocholesterol (7KC) (which accumulates in fatty tissues), to the potentially more atherogenic, 7β-hydroxycholesterol. Whether a...

Glucocorticoids are potent anti-inflammatory agents. Endogenous glucocorticoid action is modulated by 11β-hydroxysteroid dehydrogenase (11β-HSD) which interconverts active (cortisol, corticosterone) and intrinsically inert glucocorticoids (cortisone, 11-dehydrocorticosterone). 11β-HSD type 1 regenerates active glucocorticoids. 11β-HSD 1 highly expressed in the lung but its role is little explored.Immunohistochemical staining of mouse ...

Background: Bone marrow adipose tissue (BMAT) comprises >10% of total adipose mass in healthy humans and further increases in diverse clinical conditions, including obesity/diabetes, osteoporosis and following caloric restriction (CR). However, why BMAT increases during CR remains unknown. One possibility is that this is mediated by glucocorticoid (GC) excess. GC action on target tissues depends on circulating and intracellular concentrations of t...