Endocrine Abstracts

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...

Background: The 2013 Scottish Diabetes Survey demonstrated that only 22% of individuals with type 1 diabetes have optimal glycaemic control, defined as a HbA1c <58 mmol/mol. The 2014 Diabetes Improvement Plan in Scotland prioritised, ‘improving the care and outcomes of all people living with type 1 diabetes’. Scotland’s Diabetes Education Advisory Group has now been established. Accordingly, the Fife Insulin and Food Education for Diabetes (FIFE Diabetes) st...

Circulating levels of prolactin are subject to acute and long-term regulation by many factors including oestrogen and dopamine. We have studied the regulation of prolactin promoter activity in living pituitary cells using transgenic Fischer rats in which reporter gene expression is regulated by the human prolactin gene locus (hPRL-d2EGFP). We have previously identified pulsatile prolactin transcription patterns in living lactotroph cells in fetal tissue, that became stabilised...

Small cell lung cancer (SCLC) is highly aggressive with a particularly poor prognosis. This is due to tumours quickly metastasising and developing chemoresistance. SCLC tumours possess neuroendocrine properties in that they secrete prohormones such as pro-opiomelanocortin (POMC) and pro-gastrin releasing peptide (pro-GRP). These can be detected in the circulation and therefore have potential as biomarkers for prognosis and relapse. The aims of this study are; i) develop a mode...

Alternative promoters control many genes including prolactin (PRL), which in man is expressed at extra-pituitary sites controlled by an alternative promoter located 5.8 Kbp upstream of the pituitary transcription start site. Previous studies using short promoter fragments may be misleading, as the human hPRL genomic locus has many conserved far-upstream regions. To study the function of the alternative promoter, we engineered a bacterial artificial chromosome (BAC) expressing ...

Gene expression in living cells is dynamic and unstable, and fluctuations in transcription may be subject to stochastic regulation of processes including transcription factor and polymerase recruitment, and chromatin remodelling. One gene that has been shown to display dynamically variable transcription and marked heterogeneity between cells is prolactin (PRL). Time-lapse imaging of PRL-reporter gene expression in single rat pituitary GH3 cells revealed distinct long-term tran...

Pituitary development, in particular the differentiation of anterior pituitary endocrine cells, remains to be fully understood, and may have implications for adult pituitary plasticity and hyperplasia. We have used prolactin-reporter transgenic rats to characterise prolactin transcription during the appearance of newly formed lactotroph cells during fetal development.Transgenic rats with the firefly luciferase reporter gene inserted into exon 1b of a 160...