Endocrine Abstracts

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...

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...

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...

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...

We have recently reported that cannabinoids can stimulate hypothalamic and heart AMPK activity and can inhibit liver and adipose tissue AMPK activity in rats (Kola et al., JBC, 2005). These data are in accordance with the known orexigenic and adipogenic cannabinoid effects and also with their beneficial effects on the ischaemic heart. We have studied the effects of cannabinoids on AMPK activity in tissues from wild type (WT) and CB1 knockout (KO) mice to see if the CB1 ...

Mutations in AIP have been identified in a significant proportion of families with pituitary adenomas, most commonly in familial acromegaly. However, no data are available about the pituitary expression of AIP and how lack of AIP is involved in tumorigenesis.We identified 10 kindreds with AIP mutations out of 31 families. We studied RNA and protein expression of AIP in normal as well as familial and sporadic pituitary adenomas. In the normal pituitary st...

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 suggested that it is caused by a tumour suppressor gene located at 11q13. Recently mutations have been identified in a gene in some families with acromegaly alone or acromegaly and prolactinoma. The gene codes for the aryl hydrocarbon receptor interactive protein (AIP), a molecular chap...

Mutations in the AIP gene have been linked to familial cases of pituitary adenomas (Vierimaa et al, 2006). Analysis of the protein support its role as a tumour suppressor since mutations cause a loss-of-function with reduced protein interactions and over-expression of wild-type (WT) AIP reduces cell proliferation (Leontiou et al, 2008). AIP interacts with a number of interesting proteins, among them are the phosphodiesterases, PDE4A5 and PDE2A, the G proteins, Gαq and G&#...

Introduction: About 30% of all familial isolated pituitary adenoma (FIPA) and 50% of acromegaly families have a mutation in the aryl hydrocarbon receptor-interacting protein gene (AIP; Chahal, TEM, 2010). The functional role of AIP in somatotroph cells is unknown. Recently, it has been proposed that wild type AIP (wtAIP) is a tumor suppressor gene, role that is lost in the different mutant AIPs (mAIP; Leontiou, JCEM, 2008). In the adenomas, mAIPs are usually foun...