Endocrine Abstracts

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...

Prostate cancer (PCa) is driven by the androgen receptor (AR) signalling axis and begins with prostatic intraepithelial neoplasia (PIN), progressing to invasive adenocarcinoma and eventually metastatic disease. It is treated with androgen deprivation therapies, to which, in late-stage disease, tumours often become resistant and proliferation occurs in a low androgen environment. Mutation of the PTEN tumour suppressor gene is found in approximately 30% of primary human prostate...

Non-alcoholic fatty liver disease is the hepatic manifestation of the global epidemic of metabolic disease. Steroid hormones, including glucocorticoids and sex steroids, regulate metabolic phenotype, and in addition, bile acids have recently been identified as potent metabolic regulators. 5β-reductase (AKR1D1) is predominantly expressed in the liver and is a crucial regulator of steroid hormone clearance as well as bile acid synthesis. Its role in pathogenesis of metaboli...

Background: Hypercortisolism is prevalent in type 2 diabetes (T2D), but analytical and functional uncertainties prevail. Measurement of salivary cortisol is considered an expedient screening method for hypercortisolism, but its usefulness in the context of T2D is uncertain.Aim: To compare late night salivary cortisol (LNSC) with the 1 mg overnight dexamethasone suppression test (DST), which was considered ‘reference standard’, in T2D.<p cla...

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...

The late gestation increase in glucocorticoid action promotes the structural and functional maturation of the fetal heart. Metabolic maturation of cardiomyocytes involves a switch from glucose utilization as a fuel source to fatty acid (FA) oxidation. In fetal cardiomyocytes, glucocorticoids induce expression of PGC1a (a master regulator of mitochondrial capacity), lipin1 and KLF15 (genes involved in FA oxidation). We hypothesized that glucocorticoids promote the metabolic swi...

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...

Introduction: Osteoporosis and fractures are common in liver disease and fracture incidence increases after orthotopic liver transplantation (OLT). The value of bone turnover markers (BMTs) in the prediction of bone loss and fracture risk pre- and post-OLT is not known.Study design: The BMTs P1NP, osteocalcin, BALP and CTX were measured initially or in Biobank stored sera at screening and at 3, 6 and 12 months post-OLT in consecutive OLT recipients betwe...