Endocrine Abstracts

Introduction: Diagnosis of pancreatic neuroendocrine tumours (NETs) is often a challenge and involves biochemical characterisation and anatomic localisation of the tumour. Wherever feasible, curative surgical excision is the treatment of choice.Materials and Methods: Twenty four consecutive patients with pancreatic NETs were referred for consideration of surgery over a six-year period (1999–2005). Following use of multi imaging modalities to localis...

The effect of growth hormone (GH) replacement on thyroid function in hypopituitary patients has only been studied in small groups of children and adults with conflicting results.We aimed to define the effect and clinical significance of adult GH replacement on thyroid status in a large cohort of 243 patients with hypopituitarism due to various causes. 84 patients were considered euthyroid before GH treatment and 159 patients had central hypothyroidism an...

Cannabinoids and ghrelin are potent appetite stimulators. The ghrelin receptor (GHS-R1a), endocannabinoids and the cannabinoid 1 (CB1) receptor are expressed in the hypothalamus. There is evidence that the novel CB1 antagonist, rimonabant, causes weight loss by both central and peripheral effects. The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status and regulates the energy metabolism within the single cell but also at whole body level. We have shown p...

Non-islet cell tumour hypoglycaemia (NICTH) is a syndrome associated with overproduction of pro-IGF-II, a 14-18 kDa product of incomplete proteolytic cleavage of IGF-II pro-hormone, usually secreted by large mesenchymal tumours. The excess of pro-IGF-II in NICTH leads to a reduction in circulating insulin, GH, IGF-I, IGFBP-3 and acid-labile subunit (ALS) levels and to an increase in IGF binding protein-2 (IGFBP-2). IGFs and IGFBP-3 are found primarily in binary complexes of ap...

Ghrelin is an orexigenic hormone, the endogenous ligand of the previously orphan growth-hormone-secretagogue receptor (GHS-R). Recently, it has been reported that pancreatic beta-cells are replaced by ghrelin-producing cells in a diabetic mice model implicating these genes as attractive candidates in the aetiology of type 2 diabetes (T2D) (PNAS;101:2924). The ghrelin gene is located at 3p25-26 and its cognate receptor at 3q26. We aimed to test for an association of these two g...

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...

Introduction: Growth hormone (GH) replacement is widely used in the management of patients with adult-onset (AO) GH deficiency (GHD). In most cases, AO-GHD arises as a result of pituitary/peri-pituitary tumours and/or their treatment. The aim of this study was to examine the effect of GH replacement on growth/recurrence of non-anterior pituitary parasellar tumours.Methods: Fifty consecutive patients (21 males; mean age 45.9) with severe AO-GHD (peak seru...

It has been reported that both normal pituitary and pituitary tumours express PPAR gamma, a nuclear hormone receptor, the expression being much more abundant in pituitary tumours. It has also been suggested that PPAR gamma agonists, such as the thiazolidenediones, could be used as a therapeutic option for pituitary tumours. In order to investigate this further, 'Real time' PCR was used to assess PPAR gamma RNA expression, and Western blotting and immunohistochemistry was used ...

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...

Ghrelin is a brain-gut peptide originally identified in the stomach. It binds to and stimulates the growth hormone secretagogue receptor type 1a (GHS-R). The presence of ghrelin in hypothalamic tissue was studied. It has been previously established that neither the synthetic GHSs, nor the endogenous hormone ghrelin, is specific for GH stimulation: they generally also stimulate the HPA axis as well as prolactin release. Since there is no direct stimulatory effect on ACTH releas...