Endocrine Abstracts

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...

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...

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...

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...

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...

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...

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 ...

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...

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...

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...