Endocrine Abstracts

There is clear evidence from epidemiological studies that adverse conditions during pregnancy can programme changes in offspring which lead to increased risk of developing type two diabetes and obesity, two diseases associated with metabolic syndrome. Whilst earlier investigations focused on undernutrition in relation to famine, it is also relevant in the developed world to consider how dieting may programme lasting changes in the offspring.In models of ...

The decision to undertake a PhD launches you on a path of discovery, but not necessarily scientific discovery!You discover a lot about yourself. Can you survive the failed experiments, the confusion about your goals and the uncertainty about a future career?You discover a lot about working in research groups. Sometimes there is stress with your supervisor, sometimes with other members of the team.The problem ...

The majority of patients with Cushing’s syndrome are ACTH-dependent, but the diagnosis of ACTH-dependence, and then the differential diagnosis between Cushing’s disease and the ectopic ACTH syndrome, is dependent on the measurement of ACTH. In the mammalian adult anterior pituitary, POMC is cleaved into a variety of products including the ‘normal’ ACTH(1-39). In the pars intermedia (present in the human fetus and most mammals), ACTH is cleaved further by th...

The majority of patients with Cushing’s syndrome are ACTH-dependent, but the diagnosis of ACTH-dependence, and then the differential diagnosis between Cushing’s disease and the ectopic ACTH syndrome, is dependent on the measurement of ACTH. In the mammalian adult anterior pituitary, POMC is cleaved into a variety of products including the ‘normal’ ACTH(1-39). In the pars intermedia (present in the human fetus and most mammals), ACTH is cleaved further by th...

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...

Although glucocorticoids (Gc) are used to treat a range of pathologies, an individuals response to therapy varies considerably. There is a distinct correlation between certain cell types and steroid sensitivity. Aberrant glucocorticoid receptor (GR) function is well-characterised in lymphoid malignant cells but not small cell lung cancer (SCLC) (DMS79) or osteosarcoma (U2OS) cell lines, which are both Gc resistant.Previously we have shown reduced GR cont...

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...