Endocrine Abstracts

Background: Heterozygote mutations in AIP predispose carriers to young-onset pituitary adenomas, most often somatotroph or lactotroph adenomas. No other tumour type has been consistently detected in AIP mutation positive families, despite the fact that AIP is ubiquitously expressed. Current clinical and experimental data suggest that AIP is a tumour suppressor gene.Aims: To investigate the tumour suppressor role of AIP in a non-pituitary malignant cell l...

Archipelago/hCdc4/Fbw7 is the F-box protein specific for recognising and binding phosphorylated cyclin E and targeting it for ubiquitination. Mutations in Archipelago that prevent it from binding to phoshorylated cyclin E have been described in various human cancers including breast, ovarian and endometrial tumours. Previous studies have suggested that cyclin E is over-expressed in corticotroph tumours and other pituitary adenoma subtypes, and we postulated that this may be se...

Introduction: Since there is no completely effective therapy available for malignant phaeochromocytomas (PCCs) and paragangliomas, we have been investigating novel targeted therapies utilising one more benign (MPC) and one more malignant (MTT) PCC cell line. We have previously shown that the IGF1-receptor-inhibitor NVP-AEW541 led to compensatory ERK and mTORC1 up-regulation at suboptimal doses and that the dual PI3K/mTORC1-inhibitor NVP-BEZ235 also resulted in compensatory ERK...

Ghrelin is a circulating growth hormone-releasing and appetite-inducing brain–gut peptide. It needs to be acylated on its serine-3 with octanoate for its endocrine actions. The acyl-transferase that catalyses ghrelin octanoylation has been recently identified and named GOAT (ghrelin O-acyltransferase), which is coded by the MBOAT4 gene. This study aimed to investigate GOAT expression in human. The distribution of GOAT mRNA expression was studied in various human ti...

ObjectiveTo report and discuss a kindred with pathological hyperprolactinaemia.Case 1 (Proband)A 39-year old man presented in June 2003 with 3-years of erectile dysfunction (ED) and was found to have hyperprolactinaemic hypogonadotrophic hypogonadism: LH 1.0 & FSH 1.5 U/L, Testosterone 5.8 nmol/L, PRL 4154 mU/L. Pituitary function was otherwise normal. MRI demonstrated an intrasellar macroadenoma. Cabergo...

The hypothalamus plays a key role in the control of appetite and energy balance. The endogenous cannabinoids are widely distributed throughout the brain, including the hypothalamus, together with specific cannabinoid-1 (CB-1) receptors. Endogenous and exogenous cannabinoids induce hyperphagia, whereas the selective CB-1 receptor antagonist, SR 141716 (rimonabant), inhibits feeding and CB-1 knockout animals are leaner and eat less after an overnight fast. Ghrelin, the recently ...

Somatostatin and its analogues negatively regulate the growth of multiple epithelial cell types. This anti-proliferative effect occurs through multiple mechanisms, one of which is cell cycle arrest at the G0/G1 phase. p27, a cyclin-dependent kinase inhibitor, has a negative influence on cell cycle progression, and there are recent data suggesting that somatostatin increases p27 levels. We have previously shown that pituitary adenoma cells contain less p27 protein than normal p...

The opportunity to study the effects of prolonged fasting is rare. In this study we recorded anthropometric, biochemical and endocrine changes during the refeeding period following a 44 day fast, and compared them with results from 16 age-, sex- and body mass index (BMI)-matched controls.The index subject took only water to drink during the fast. He lost 24.5kg changing his BMI from 29 to 21.6. He underwent careful slow refeeding for the first 4 days usi...

It has been postulated that ACTH might modulate its own secretion by a negative feedback loop and we have recently found that the ACTH receptor (MC2R) is present in both normal and tumorous human corticotrophs. In this study we investigated the expression of the ACTH receptor in mouse and rat pituitary tissue as well as mouse pituitary tumour (AtT20) cells and studied the effect of Synacthen (ACTH [1-24]) on ACTH secretion, cAMP release and cell proliferation in AtT20 cells. M...

In addition to its original growth hormone-releasing function,ghrelin has been shown to exert a variety of effects on metabolism,specifically in terms of the regulation of body habitus and fat. Itincrease food intake and body weight, and regulates energyhomeostasis: it also increases glucose levels, reduces insulinsecretion and regulates downstream insulin signa...