Endocrine Abstracts

Background: Pituitary adenomas are relatively common in the general population, but the pathogenesis of these tumours remains largely unknown. Recently, germline mutations have been described in the AIP (aryl hydrocarbon receptor interacting protein) gene in several patients with familial isolated pituitary adenomas (FIPA). This gene is located on chromosome 11q13 and loss of heterozygosity at this locus as well as functional data from our group demonstrates a tumour suppresso...

Background: Pituitary adenomas usually occur as sporadic tumours, but familial cases are increasingly identified. Patients of 15–40% with familial-isolated-pituitary-adenoma (FIPA) harbour germline mutations in the aryl-hydrocarbon receptor interacting gene (AIP). AIP is thought to act as a tumour suppressor gene, with loss of heterozygosity shown in pituitary tumour samples at the 11q13 locus, where AIP is located. Previously we have shown AIP has properties consistent w...

There are controversial data on the beneficial/detrimental effects on the cardiovascular as well as on the metabolic system by the sex hormone testosterone. Recent data support the hypothesis that low levels of androgens are associated with adverse cardiovascular risk factors including an atherogenic lipid profile, obesity, insulin resistance and hypertension. AMPK is a sensor of energy balance at both the cellular and whole-body level. Once activated by low energy status, it ...

Background: Recently mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene have been found to occur in familial and sporadic somatotroph adenomas. These tumours tend to respond less well to somatostatin analogues, are diagnosed at an earlier age and behave more aggressively. AIP is expressed in sporadic somatotroph adenomas (Leontiou, JCEM, 2008).Aim: To evaluate the change in AIP immunostaining in sporadic acromegaly patients treated...

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant negative disorder characterised by the occurrence of multiple adenomas including hyperplasia and/or neoplasm of the parathyroid glands, pancreatic islets and pituitary glands. Germline mutations in the menin gene predispose to the MEN1 syndrome; however, about 10–20% of patients with MEN1 do not have a detectable menin mutation. Recently, a mouse strain with a MEN1-like phenotype has been re...

Background: AMPK is a metabolic enzyme regulating the energy supply of the cell but it has antiproliferative effects as well via the up-regulation of the p53-p21 axis and inhibition of the mTOR-pathway. Somatostatin (SST) analogues reduce hormone secretion from somatotroph adenomas and tumour growth inhibition can also be achieved. SST affect several signalling pathways including the mTOR-pathway. mTOR is a mediator of a pro-proliferative pathway that can be inhibited by activ...

Background Ghrelin stimulates cell proliferation in a number of tissues including pituitary. AMPK, a heterotrimer kinase enzyme, is an important sensor and regulator of cellular energy balance. We have shown that ghrelin can change AMPK activity in various tissues and this mechanism could play a role in its metabolic effects. AMPK has recently been established to strongly inhibit cell proliferation and tumorigenesis. We therefore hypothesised that ghrelin stimulates cell proli...

Hypothalamic MC4R receptors are Galphas-coupled GPCR’s that mediate the satiety response to αMSH. MC4R expression predominates in the PVN/VMH regions of the hypothalamus, regulating satiety gene expression (e.g. Bdnf). Human MC4R mutations often result in compromised Galphas-cAMP-PKA signalling and obesity onset. However, downstream signalling pathways have yet to be elucidated. We have investigated the potential for αMSH to stimulat...

Background: Ghrelin stimulates cell proliferation in a number of tissues including pituitary. AMPK, a heterotrimer kinase enzyme, is an important sensor and regulator of cellular energy balance. We have shown that ghrelin can change AMPK activity in various tissues and this mechanism could play a role in its metabolic effects. AMPK has recently been established to strongly inhibit cell proliferation and tumorigenesis. We therefore hypothesised that ghrelin stimulates cell prol...

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...