Endocrine Abstracts

Introduction: Adenosine monophosphate-activated protein kinase (AMPK) is a regulator of cellular and systemic energy homeostasis. Many of the changes seen in glucocorticoid excess correspond to the metabolic steps regulated by AMPK. In the hypothalamus and adipose tissues, glucocorticoids and cannabiniods share the same tissue specific effects on AMPK activity. Cannabinoids have central orexigenic and peripheral metabolic effects via the cannabinoid receptor type 1 (CB1). The ...

Cannabinoids are known to exert effects throughout the endocrine system, including in the anterior pituitary. Whilst cannabinoid receptors (CB1 in particular) are expressed in numerous tissues, expression and function of an endocannabinoid system within specific anterior cell types has not been investigated. We have used well-characterised gonadotroph (LβT2 and αT3-1) and somatolactotroph (GH3) cell lines to establish the expression and functional role for cannabinoi...

Recently the Aryl hydrocarbon receptor – interacting protein (AIP) gene attracted attention as a novel gene linked to familial cases of acromegaly. In Malta the predicted prevalence of pituitary adenomas is particularly high, 4.67 per 10,000 population, thus suggesting a genetic predisposition.Fourty seven maltese patients with acromegaly were screened for germ-line mutations in the AIP gene. Pituitary tumour tissue, removed during transphenoidal su...

Background: Recently, germline mutations in the aryl-hydrocarbon-receptor-interacting-protein (AIP) gene have been found to occur in familial and sometimes in early onset sporadic somatotroph adenomas. These tumours tend to respond less well to somatostatin analogues (SSA). It has been shown previously that AIP can upregulate the transcription factor Zac1 in liver cells, and we were able to also demonstrate this in pituitary cells. On the other hand, Zac1 is upregulated in res...

Adenosine 5′-monophosphate-activated protein kinase (AMPK), a regulator of energy homeostasis, has a central role in mediating the appetite-modulating and metabolic effects of many hormones and neuromodulators. We previously demonstrated similar neuroendocrine activation of AMPK in bone-forming osteoblasts. In this study, we tested whether stimulation of AMPK activity in osteoblasts plays a role in their function and whether deletion of the catalytic AMPKα1 subunit,...

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...