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...

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 ...

Background: Ghrelin was recently discovered as the natural ligand for the G protein-coupled growth hormone secretagogue receptor and induces GH release through GHS-R1a. The octanoylation of its third serine residue is responsible for GH release and receptor binding. A variant of ghrelin devoid of this modification, desoctanoyl-ghrelin, can neither bind to the receptor nor induce GH release. Ghrelin has also been shown to effect cellular proliferation, being pro-proliferative i...

A number of single nucleotide polymorphisms (SNPs) have been identified in the GHRH receptor gene. Two of these SNPs, A57T and V225I, have been found to cause an increased cAMP response to GHRH stimulation in vitro, and it has been suggested that they may be associated with the abnormal biochemistry in patients with somatotroph adenomas. The objective of this study was to clarify the frequencies of these SNPs in the normal population and in subjects with short stature. The sub...