Searchable abstracts of presentations at key conferences in endocrinology

ea0034p171 | Neoplasia, cancer and late effects | SFEBES2014

Neuroendocrine biomarkers change with treatment in small cell lung cancer

Meredith Suzanne , Bryant Jennifer , Babur Muhammad , Riddell Philip , Williams Kaye , White Anne

Small cell lung cancer (SCLC) is distinguished by its neuroendocrine phenotype and secretion of hormone biomarkers. Tumours initially respond well to therapy but almost invariably relapse with a therapy-resistant phenotype. We have previously described pro-opiomelanocortin (POMC) as a potential biomarker of SCLC. In this study, we investigated how POMC acts as a biomarker of tumour response to treatment.SCLC cells (DMS 79) were injected subcutaneously in...

ea0031oc4.3 | Obesity, metabolism and bone | SFEBES2013

Adult offspring of undernourished sheep exhibit epigenetic alterations in HPA axis glucocorticoid receptor

Begum Ghazala , Stevens Adam , Oliver Mark , Jaquiery Anne , Harding Jane , Challis John , Bloomfield Frank , White Anne

Maternal programming increases the risk of alterations in the offspring’s HPA axis. Previously we showed that maternal undernutrition in sheep induces epigenetic changes in the glucocorticoid receptors (GR) within hypothalamic energy balance pathways, without affecting HPA axis GR. However, these studies focussed on fetal tissues1. Here, we investigated whether GR is epigenetically altered in the HPA axis of adult offspring to determine the status of the pathwa...

ea0031p185 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2013

Knockdown of brain 11β-HSD1 does not lower body weight or improve insulin sensitivity

Harno Erika , Cottrell Elizabeth C , DeSchoolmeester Joanne , Turnbull Andrew V , Leighton Brendan , White Anne

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...

ea0030p38 | (1) | BSPED2012

Cushing's syndrome due to POMC secretion from an abdominal yolk sac tumour in a 2 year old child

Gevers Evelien , Shah Pratik , Meredith Suzanne , Torpiano John , Slater Olga , White Anne , Dattani Mehul

Cushing’s syndrome due to ectopic ACTH production is extremely rare in childhood. Ectopic ACTH secretion is most often due to tumours in the chest, but rare cases of carcinoid tumours, neuroblastoma, phaeochromocytoma and pancreatic and ovarian carcinoma have been reported. We describe a 2 year old girl with ectopic Cushing’s syndrome due to a malignant epithelial abdominal tumour producing POMC. She presented with rapid weight gain, hypertension, body odour, letharg...

ea0029oc4.2 | Pituitary Basic | ICEECE2012

Transcriptional regulation of prolactin by oestrogen in vivo

Patist A. , Featherstone K. , Spiller D. , Semprini S. , McNeilly J. , McNeilly A. , Mullins J. , White M. , Davis J.

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...

ea0028p165 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2012

Epigenetic changes in hypothalamic energy regulating pathways implicated in programming of adult offspring

Begum Ghazala , Stevens Adam , Jaquiery Anne , Challis John , Bloomfield Frank , White Anne

There is increased prevalence of obesity and diabetes in offspring from mothers subjected to adverse conditions during pregnancy. Our previous work demonstrated that maternal undernutrition causes epigenetic changes in hypothalamic energy regulating networks in foetal sheep. We hypothesise that these changes will persist into adulthood. Therefore, this study examined the impact of maternal undernutrition on epigenetic and mRNA expression of hypothalamic regulators of energy ba...

ea0021oc1.2 | Diabetes and metabolism | SFEBES2009

Moderate maternal undernutrition results in epigenetic changes in the fetal hypothalamic feeding centres, but not in the fetal HPA axis

Begum Ghazala , Stevens Adam , Oliver Mark , Connor Kristin , Challis John , Bloomfield Frank , White Anne

Maternal undernutrition influences the development of obesity and diabetes in the adult offspring. Previous work has shown that moderate maternal undernutrition may alter the stress–response of the hypothalamic–pituitary–adrenal (HPA) axis; however, it is not clear if this is the mechanism for consequent obesity in offspring.The aim of this study was to analyse epigenetic changes in the POMC and GR genes in the pituitary as markers of HPA ...

ea0021p182 | Diabetes and metabolism | SFEBES2009

Deficiency in 11β-hydroxysteroid dehydrogenase type 1 reduces systemic inflammation and inflammatory cell infiltration in atherosclerotic lesions of ApoE−/− mice

Kipari Tiina , Man Tak-Yung , Hadoke Patrick , White Christopher , Chapman Karen , Seckl Jonathan

High plasma levels of glucocorticoids cause metabolic disease (central obesity, hypertension, diabetes) and increase risk of cardiovascular disease. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates glucocorticoids in intact cells, converting inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone in rodents). Recent work has shown the pathological importance of elevated adipose tissue 11β-HSD1 expression in develo...

ea0021p186 | Diabetes and metabolism | SFEBES2009

Circadian rhythmicity is altered in hepatic corticosterone-related genes from diet induced obese mice

Harno Erika , Yu Alice , Brown Henry , Turnbull Andrew , Leighton Brendan , White Anne

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...

ea0021p221 | Endocrine tumours and neoplasia | SFEBES2009

Pro-opiomelanocortin is a novel biomarker for small cell lung cancer

Stovold Rachel , Stevens Adam , Ray David , Sommers Paula , Dive Caroline , Blackhall Fiona , White Anne

Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumour that shows early metastasis and resistance to chemotherapy. Current biomarkers focus on prognosis and diagnosis but there is a need to find novel biomarkers, which could, for example, identify patients at risk of cerebral metastases.Pro-opiomelanocortin (POMC), the precursor of ACTH is a well-recognised biomarker of the ectopic ACTH syndrome1, of which SCLC is the most preval...