Endocrine Abstracts

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...

A provisional diagnosis of paroxysmal atrial fibrillation with normal blood pressure and echocardiogram was made in a 58 years old man. He described ‘funny turns’ on standing during which he would become sweaty, tremulous with palpitations and headache and facial flushing preceded by pallor. The patient was otherwise fit and healthy with a BMI of 27.3 kg/m2; he used to drink about 15 pints of beer per week and smoke 11 cigarettes daily for the last 40 year...

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...

Objective: To establish the prevalence of Syndrome X in women with Polycystic Ovary Syndrome (PCOS) and determine which sonographic features of PCO best predict syndrome X.Background: Recently, the third report of the USA national cholesterol education program expert-panel on the detection, evaluation and treatment of high blood cholesterol in adults specifically identified syndrome X, a combination of insulin resistance and compensatory hyperinsulinaemi...

The cell cycle occupies a pivotal role in the control of cellular proliferation, a critical point being activation of CyclinE which is held in check by the inhibitor p27. CyclinE is targeted for degradation by the F-box protein Archipelago (Ago/Fbw7/cdc4), while p27 is exported out of the nucleus by Jun activation domain-binding protein 1 (Jab1). Over-expression of CyclinE has been reported in breast cancer. We have now explored the role of Jab1 and Ago in mediating changes in...

Mitogenic signaling by receptor tyrosine kinases that involve increased activity of phosphatidylinositol-3-kinase (PI3K) and over-activation of protein kinase B (PKB/Akt) triggers a cascade of responses that drive tumour progression in a variety of human cancers. Some of these events have been associated with diminished expression of the cell cycle inhibitor p27 through inhibition of a Forkhead transcription factor (FKHR-L1) by Akt, while some others have recently been reporte...

BACKGROUND: Ghrelin is a novel 28-amino acid peptide which was isolated from the rat stomach and has now been shown to have a widespread tissue distribution. Ghrelin is the endogenous ligand of the growth hormone secretagogue receptor type 1a (GHS-R1a), and stimulates growth hormone (GH) release via the hypothalamus as well as by a direct action on the pituitary GHS-R1a. Ghrelin and the GHS-R1a also coexist within the pituitary. There are conflicting data regarding the effects...

The proto-oncogene Gsalpha has been implicated in a significant minority of somatotrophinomas, but the search for candidate oncogenes in the remaining somatotrophinomas, and in the great majority of other types of benign pituitary adenomas, has so far been unsuccessful. Microarray-based comparative genomic hybridisation (microarray-CGH) is a novel DNA microarray technique that has been shown to identify gain or loss at the gene level, and has been proposed as a tool to screen ...

The ACTH receptor (ACTH-R) is the second member of the melanocortin receptor family that includes five seven-transmembrane G protein-coupled receptors, and has been shown to be predominantly expressed in the adrenal cortex. It has been postulated that ACTH may regulate its own secretion through ultra-short loop feedback within the pituitary, and as ACTH-secreting adenomas are characterised by resistance to glucocorticoid feedback, they may also have dysregulated ACTH feedback....