Endocrine Abstracts

Background: 20% of the familial isolated pituitary adenoma (FIPA) population harbour an aryl hydrocarbon receptor-interacting protein (AIP) gene mutation. The recognition of whether a variant is pathogenic can be difficult, in cases where the observed change does not lead to a truncated protein. Segregation with disease in a family, in silico predictions, loss of heterozigosity in the tumour, in vitro functional studies and screening of the variant in controls may help in asce...

Introduction: The hypothalamic hormone orexin-A (OXA) increases food and water intake, regulates the sleep-wake cycle, muscle tone and energy balance. AMP-activated protein kinase (AMPK) is an important metabolic regulator with direct hypothalamic orexigenic and diverse peripheral effects including fat tissue and muscle.Aims: We aimed to study the influence of OXA on the activity of AMPK in the hypothalamus, subcutaneous and visceral adipose tissues, and...

Background: Somatostatin analogues are very useful in the treatment of symptomatic neuroendocrine tumours, but effects on proliferation remain unclear. Overexpression of the proto-oncogene protein kinase Akt has been demonstrated in certain endocrine tumours, and activates downstream proteins including mTOR and p70S6K, which play a significant role in cell growth and proliferation. We have therefore explored the site of action of somatostatin in causing inhibition of prolifera...

Background: Cushing’s syndrome results from chronic exposure to excessive levels of glucocorticoids (GC). The clinical manifestations associated with hypercortisolaemia are variable and differ widely in severity, including hypertension, apparent obesity and metabolic aberrations such as diabetes, dyslipidaemia, ultimately leading to changes similar to the metabolic syndrome. We hypothesised that GC might influence the expression of the genes involved in lipogenesis and gl...

Objective: Neurotensin is an anorexigenic peptide produced mainly in the N-cells of the ileum; levels are decreased in obese subjects and increase after bariatric surgery. This study is the first to compare the baseline and postoperative levels of neurotensin in patients after gastric bypass, gastric banding, and non-operated controls, respectively, during long-term follow-up.Patients and Methods: Overnight fasting plasma neurotensin levels were measured...

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...

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...