Endocrine Abstracts

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...

Introduction: Acromegaly is the most genetically determined pituitary disease.Objectives: We studied the prevalence of syndromic disease and germline mutations (AIP, MEN1, GNAS, PRKAR1A, CDKN1b) in a cohort of unselected, consecutive patients with acromegaly.Materials and methods: A total of 133 patients (79 females, 54 males, age range 16–75 years) with somatotroph pituitary neuroendocrine tumor who were studied at t...

Introduction: Aryl hydrocarbon receptor interacting protein (AIP) is a multifunctional co-chaperone protein with wide-ranging effects. It acts as a tumour suppressor in the pituitary, but may have other roles including oncogenic function in other tissues. To explore the molecular mechanisms, we have performed transcriptomic and phosphoproteomic analysis of Aip-knockout mouse embryonic fibroblasts (Aip-KO MEFs) cells and integrated these data sets.<p class=...

A 16-year-old female presented with secondary amenorrhoea. Menarche was age 14 years and periods were less frequent over the preceding 12 months. There was no galactorrhoea, headache or visual field disturbance and no known family history of pituitary disease, tall stature or infertility. There were no clinical signs of Cushing’s disease or acromegaly and visual fields were full to confrontation. Height was 160 cm. Investigations showed a prolactin of 2,452 mIU/l (RR 102-...