Endocrine Abstracts

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...

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...

While primary hyperparathyroidism is most commonly due to a parathyroid adenoma, very occasionally it may be secondary to a parathyroid carcinoma. A substantial minority of parathyroid adenomas are due to mutations or transpositions in genes in involved in the regulation of the cell cycle. In particular, at the cell cycle checkpoint which regulates exit from G1 phase, there is an interaction between the cyclins and cyclin-dependent kinases (CDKs); specifically, cyclin D intera...

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...

Disruption of the normal cell cycle is one of the most frequent alterations in tumour cells, contributing to uncontrolled cell proliferation during tumour development. The CDK inhibitor p27 plays a pivotal role in controlling cell proliferation during development and tumourigenesis, and has been implicated in tumorigenesis in rats. Previous studies have demonstrated changes in p27 protein expression, in human pituitary tumours,especially in corticotroph tumours, where p27 prot...

Aim: Clinical acromegaly is characterized by high GH secretion in the presence of high circulating IGF-I levels. We therefore hypothesized that the physiological IGF-I-GH negative feedback loop may be reset in somatotroph adenomas, and we investigated the role of type 1 IGF receptor (IGF-R) and GH receptor (GHR) by quantifying mRNA expression in somatotroph tumours, and investigated the possible presence of mutations of the GHR gene.Methods: Pituitary t...

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 ...