Endocrine Abstracts

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...

In addition to its original growth hormone-releasing function,ghrelin has been shown to exert a variety of effects on metabolism,specifically in terms of the regulation of body habitus and fat. Itincrease food intake and body weight, and regulates energyhomeostasis: it also increases glucose levels, reduces insulinsecretion and regulates downstream insulin signa...

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...

MIF can override the anti-inflammatory actions of glucocorticoids during immune response, and thus is an important pro-inflammatory factor. The presence of MIF in the cytoplasm of adenomatous cells of the anterior pituitary has been described, and high levels of MIF in other rapidly-proliferating tissues have been demonstrated. It is hypothesized that MIF release from these cells is influenced by the hypothalamo-pituitary-adrenal axis, and that ACTH and MIF are released simult...

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...

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....

Carney complex (CNC) is an autosomal dominant multiple neoplasia syndrome featuring cardiac, endocrine, cutaneous and neural tumours, as well as a variety of pigmented lesions of the skin and mucosa. Pituitary GH-secreting tumours are found in approximately 10% of patients with CNC. One of the genes responsible for CNC, the PRKAR1A gene, located on human chromosome 17q22-24, has recently been cloned. This represents a putative tumour suppressor gene, coding for the type 1alpha...

BACKGROUND: Cell cycle dysregulation is one of the defining features of cancer. Cyclin-dependent kinase 4 (CDK4), together with its regulatory subunit Cyclin D, governs cell cycle progression in G1 phase. CDK4 is in turn regulated by cyclin-dependent kinase inhibitors, including p16INK4A (CDKN2A). Dysregulation of the INK4A/CDK4/cyclin D complex has been established in different a variety of types of human tumours. Dominant mutations affecting codon 24 of the CDK4 gene (replac...

Introduction: Patients with acromegaly have an increased risk of colorectal cancer and pre-malignant adenomatous polyps; however the frequency of colonoscopic screening remains unclear.Aims: To determine optimum frequency for repeated colonoscopy of acromegalic patients.Methods: Since 1992, 254 patients (mean age 56.6 years) at our centre have undergone at least one fibre-optic colonoscopic surveillance; 156, 60 and 15 patients hav...

Pituitary adenomas are present in ∼25% of autopsy samples, and recent studies have also suggested that clinically important pituitary adenomas are some 5 times more common than previously recognised. Acromegaly is almost always due to a sporadic growth-hormone secreting pituitary adenoma, but familial acromegaly has been reported occasionally. Linkage and loss of heterozygosity studies have shown that it is caused by a tumour suppressor gene located at 11q13; very recent...