Endocrine Abstracts

Sporadic pituitary tumours are generally benign tumours in which the none of the oncogenes or tumour suppressor genes classically mutated in other cancers are commonly mutated, nor are there frequent changes in genes associated with genetic endocrine neoplasia syndromes. Such tumours are associated with excessive but not completely unregulated proliferation, implicating a possible abnormality in a cell signalling pathway in their pathogenesis. Recently, the serine/threonine ki...

Background: Extracellular signal-regulated kinase (ERK) cascades are key signaling pathways involved in regulation of normal cell proliferation, survival and differentiation. Abberrant regulation of the ERK pathway contributes to tumourigenesis. The ERK signalling cascade partially controls transcription of the cell cycle regulator cyclin D1 and also expression and protein stability of the c-Myc proto-oncogene.Methods: Western Blotting was used to invest...

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...

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...

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....

While pituitary adenomas (PA) usually occur as a sporadic disease, an increasing number of patients are recognised with a family member also suffering from a PA. If no other syndromic features are present, these families are categorised as FIPA. In published studies, 20% of the FIPA families, 20% of sporadic childhood and 13% of sporadic young-onset (≤30 years) acromegaly patients carry a germline AIP mutation. As familial disease is more aggressive, family scre...

In the late 1700s, a 22 y patient suffering from pituitary gigantism died and his skeleton was deposited in a medical museum. A contemporary etching showed him standing alongside a set of giant twin brothers who were believed to be his cousins. The existence of such a rare disorder within closely related family members indicates to modern science a genetic dimension to their disease. In 1909 Cushing opened the skull and he found a greatly enlarged pituitary fossa. We identifie...

Pituitary adenomas are commonly occurring lesions, only some of which will result in clinically significant disease. The underlying molecular changes leading to monoclonal cell proliferation with self-limited growth in the majority of cases, and continuous growth in a small proportion, are currently unknown. While hormonal influences are clearly important additional factors, the primary abnormality will ultimately lead to up-regulation of the cell cycle machinery. Hormonal fee...

Numerous growth factors, oncogenes, tumour suppressor genes and hormonal influences have been implicated in pituitary tumorigenesis. We have demonstrated that the PI3K-Akt pathway is upregulated in pituitary tumours and since Akt is a major downstream signalling molecule of growth factor-liganded tyrosine kinase receptors it is possible that an abnormality at this level could be the primary driver of pituitary tumorigenesis. The serine/threonine kinase B-Raf functions as a dow...

Ghrelin is a novel growth hormone-releasing peptide, recently identified in the rat stomach as the endogenous ligand for the growth hormone secretagogue-receptor (GHS-R). Previously, regulation of GH release was thought to occur primarily via a phasic interaction between two hypothalamic neuropeptides, GHRH and somatostatin. It is now thought that ghrelin is an important third factor in the regulatory pathway. In addition to its GH-releasing activity ghrelin may have other act...