Endocrine Abstracts

Synthetic glucocorticoids (GCs) are widely used in clinical practise to treat various inflammatory disorders including rheumatoid arthritis, asthma and some malignancies. Although generally well tolerated, long-term, especially high dose use can lead to metabolic side effects. We have developed a mouse model of GC treatment in drinking water, using corticosterone (Cort, the endogenous GC in rodents), which recapitulates many of the side-effects in patients treated with GCs. Af...

Inhibition of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) as a means of reducing tissue corticosteroids is showing marked potential as a treatment for type 2 diabetes. However, reduction in tissue corticosteroids may lead to upregulation of the HPA axis. Therefore this study investigates the effect of 11β-HSD1 inhibition on HPA axis biomarkers and examines whether time of dosing impacts on the biomarkers.C57Bl6/Jax mice were fed 60% kcal...

Glucocorticoids act on several major neuropeptide networks in the hypothalamus which are important for regulation of energy balance and insulin sensitivity. Active glucocorticoids (cortisol/corticosterone in humans/rodents) can be regenerated from their inactive forms by the enzyme 11β-hydroxysteroid dehydrogenase type one (11β-HSD1) which is expressed in the hypothalamus. Therefore we decreased 11β-HSD1 expression in the brain to investigate the role of regener...

Increased corticosterone (cortisol in humans) in liver has important adverse effects on glucose metabolism and is therefore a target for diabetes treatments. The functional effects of corticosterone depend on circulating levels as well as tissue regeneration by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) and inactivation by steroid 5-α-reductase type I (5αR). This study investigates how obesity affects diurnal changes in circulating corticosterone, the ge...

Glucocorticoids are widely prescribed therapeutic agents, however long term treatment can cause increased morbidity from adverse metabolic events, including weight gain and hyperglycaemia. The mechanisms and site of action which underpin these side-effects are not fully understood. The aim of this study was to characterise phenotypic, biochemical and neurohormonal responses in mice administered corticosterone, with a particular focus on changes seen in the early stages of chro...

Glucocorticoids (GCs) are widely prescribed to treat a number of inflammatory and autoimmune conditions. However, patients receiving GCs often develop adverse metabolic effects such as hyperphagia leading to weight gain and hyperglycaemia. Little is known about the central effects of GCs; however they can act in the hypothalamic arcuate nucleus (ARC), a region involved in the integration of other energy regulatory hormones such as leptin, insulin and ghrelin. Therefore, the ai...

Glucocorticoids (Gcs) are used in the treatment of inflammatory disorders including asthma and rheumatoid arthritis. However, long-term use can cause metabolic side-effects including obesity and diabetes. Previous studies have shown that Gcs increase Agrp expression and that AgRP/NPY/GABA (ANG) neurons can regulate appetite and insulin sensitivity. To investigate the effects of chronic Gc treatment directly on ANG neurons, we crossed AgRP-IRES-Cre with GR...

Glucocorticoid (Gc) excess, either from endogenous overproduction in disorders of the hypothalamic-pituitary-adrenal axis or exogenous medical therapy, is recognized to cause adverse metabolic side effects including obesity, hyperphagia, and hyperglycemia. The Gc receptor (GR) is widely expressed in the brain including the hypothalamus which is known to regulate energy balance. We have previously established through the administration of corticosterone (Cort) in the drinking w...

Glucocorticoids (Gcs) are widely prescribed to treat a number of conditions, such as arthritis and asthma. However, patients receiving Gcs often develop metabolic complications such as obesity and hyperglycaemia. The aim of this study was to investigate the molecular mechanisms in the hypothalamus which drive these adverse effects. Male C57BL/6J mice were given ad libitum access to either corticosterone (CORT; 75 μg/ml) or vehicle (V; 1% ethanol) in their drinkin...

Background and objective: The prevalence of obesity is increasing worldwide and it is known that intra-uterine experience can program metabolic disorders. The hypothalamic appetite regulatory system is a key target of developmental programming by maternal nutrition. Therefore, the aim of this study was to investigate the effects of maternal overnutrition on the expression of hypothalamic genes controlling energy homeostasis.Research design: Eight week ol...