Endocrine Abstracts

NAD+, as well as its phosphorylated form NADP+, are best known as electron carriers and co-substrates of various redox reactions essential to the cellular processes of energy metabolism and biosynthesis. Dynamic changes in NAD+ availability can trigger sensors, such as the protein deacetylase sirtuin enzymes, to adjust cellular and tissue physiology in response to changes in nutrient availability and energy demand. These signalling processes consume NAD+ and release nicotinami...

Glucocorticoids (GCs) have physiological actions in almost all tissues, classically mediated by the GC receptor. The potent effects of GCs upon metabolic phenotype are best exemplified in patients with circulating GC excess (Cushing’s syndrome), who develop central (visceral) obesity, insulin resistance, myopathy, hypertension and in some cases overt type 2 diabetes (T2DM) and non alcoholic fatty liver disease (NAFLD). GCs are one of the most frequently prescribed class o...

We all want to be earnest and successful basic researchers; usually this means running a group and this can be difficult when as an academic you will also have administrative duties, committees to attend and teaching to give. And as a rounded and fulfilled human being you will have a personal life that rewards in many other ways, such as a passion for sport, family or other activities. Life is and should be fluid, so it is unrealistic and unrewarding to schedule an equal numbe...

The novel congenital adrenal hyperplasia variant, ‘apparent’ cortisone reductase deficiency (ACRD), has highlighted the significance of subcellular redox potential in regulating glucocorticoid hormone action. In ACRD, there is an attenuation of perceived glucocorticoid (GC) concentrations which results in up-regulation of adrenal androgen production as a consequence of increased hypothalamic-pituitary-adrenal (HPA) activity. We have recently identified mutations in t...

Ligand binding of the glucocorticoid receptor (GR) initiates recruitment to GR Response Elements (GRREs). GR transcriptional activation of genes manifests many of the pleiotropic actions attributed to glucocorticoids. However, excessive exposure to GCs produces detrimental impacts, shifting GR behaviour and driving dysregulated metabolic states. Moreover, GR, its interacting partners, and influencing proteins remain ambiguous. Poly-(ADP-ribosyl) polymerase 1 (PARP1) is a chrom...

Introduction: Glucocorticoids are vital for regulating metabolic processes, as well as use in medical treatments. However chronic glucocorticoid excess is known to cause negative metabolic effects including hyperglycaemia, muscle atrophy and fat accumulation. The effect on energy metabolism and metabolic rate remains undefined and merits investigation in both male and female mice.Methods: 20 male and 20 female C57BL/6J mice were randomly assigned to a co...

Objective: Therapeutic glucocorticoids (GCs) are commonly used in the treatment of chronic inflammatory disease. Unfortunately, their long-term administration is associated with deleterious systemic side effects including muscle atrophy. 11 beta-hydroxysteroid dehydrogenase type 1 (11βHSD1) activates glucocorticoids within muscle, is increased with inflammation, and has previously been shown to mediate GC induced muscle wasting. We examined the role of 11 beta-hydroxyster...

Glycogen storage disease type 1b is a metabolic disorder resulting in an inability to shuttle glucose-6-phosphate across the sarcoplasmic/endoplasmic reticulum (SR/ER) lumen. Mutation of the SoLute Carrier 37a4 (slc37a4) or glucose-6-phosphate transporter (G6PT) gene responsible for the distribution of G-6-P across this membrane leads to, hypoglycemia, hepatic glycogen accumulation, hyperlipidemia, resulting in life-limiting outcomes including growth retardation and neutropeni...

Hexose-6-phosphate dehydrogenase is an important factor in setting the redox status of the endo-/sarcoplasmic reticulum (ER/SR) lumen by generating the NADPH:NADP+ ratio for 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) mediated glucocorticoid (GC) activation. H6PDH knockout mice (H6KO) clearly demonstrate the obligate nature of 11β-HSD1 for H6PDH, and display a vacuolating of type IIb fiber myopathy, elevated glycogen storage and type II to type...

Glucocorticoid (GC) excess adversely affects many aspects of skin homeostasis, characteristics of which are also seen during ageing (e.g. poor wound healing). The mechanisms underlying this remain unclear. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates cortisol, independently of circulating concentrations, and we have previously demonstrated increased 11β-HSD1 expression in human dermal fibroblasts (HDF) from aged donors. We have now e...