Searchable abstracts of presentations at key conferences in endocrinology

ea0094p156 | Adrenal and Cardiovascular | SFEBES2023

Glucocorticoid receptor and PARP-1 genomic binding changes in response to corticosterone excess in mice

Heaselgrave Samuel , Lavery Gareth , Doig Craig

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...

ea0077p198 | Metabolism, Obesity and Diabetes | SFEBES2021

Corticosterone excess alters metabolic rate in male and female C57BL/6J mice

Heaselgrave Samuel , Heising Silke , Morgan Stuart , Morton Nicholas , Lavery Gareth

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...

ea0086p155 | Adrenal and Cardiovascular | SFEBES2022

Glucocorticoid Excess Disrupts the NAD+ Metabolome Within Skeletal Muscle in Male and Female C57BL/6J Mice

Heising Silke , Heaselgrave Samuel , Morgan Stuart , Kabli Ali , Doig Craig , Tsintzas Kostas , Lavery Gareth

Introduction: Glucocorticoid excess (GE) causes severe metabolic dysfunction within skeletal muscle (SM) which includes reduced muscle accrual and increased proteolysis. The NAD+ metabolome is crucial for SM health and metabolic function, however, whether this is disrupted by GE remains unknown.Methods: Male and female C57BL/6J mice (n=12) were treated with a vehicle control or corticosterone (100 mg/l) ad libitum via drinking water for 3 weeks ...

ea0086oc4.6 | Adrenal and Cardiovascular | SFEBES2022

Glucocorticoid excess elevates metabolic rate via a 11β-HSD1 dependent mechanism in C57BL/6J mice

Heaselgrave Samuel , Heising Silke , Morgan Stuart , Kabli Ali , Sagmeister Michael , Hardy Rowan , Doig Craig , Morton Nicholas , Tsintzas Kostas , Lavery Gareth

Introduction: Glucocorticoids are vital metabolic regulators. However, glucocorticoid excess (GE) causes severe metabolic dysfunction, ultimately leading to Cushing’s Syndrome. This dysfunction is often dependent on the presence of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Whether GE also alters metabolic rate, and whether this is also dependent on 11β-HSD1, remains unclear.Methods: Male and female wild-type (WT) ...

ea0086p157 | Adrenal and Cardiovascular | SFEBES2022

Depleting NAD+ pools specifically in the endoplasmic reticulum lumen impairs 11β-hydroxysteroid dehydrogenase activity

Kabli Ali , Heising Silke , Heaselgrave Samuel , Elhassan Yasir , Hardy Rowan , Stromland Oyvind , Ziegler Mathias , Morgan Stuart , Hodson David , Lavery Gareth

Introduction: The endoplasmic reticulum (ER) lumen enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) obtains NADPH from hexose-6-phosphate dehydrogenase to reduce cortisone to the active glucocorticoid cortisol. Cells depleted in NAD+ (parent molecule of NADPH) have impaired 11β -HSD1 activity, which can be rapidly rescued with supplementation of the NAD+ precursor nicotinamide riboside. This suggests the existence of an ER-specific pathway to NAD(P)(H)....