Endocrine Abstracts

Background: Heterozygote mutations in the aryl hydrocarbon receptor-interacting protein (AIP) predispose carriers to young-onset pituitary adenomas, most often somatotroph or lactotroph adenomas. No other tumour type has been consistently detected in AIP mutation positive families, despite the fact that AIP is ubiquitously expressed. Current clinical and experimental data suggest that AIP is a tumour suppressor gene.Aims: To investigate the tumour suppre...

Background: Aryl hydrocarbon receptor interacting protein (AIP) mutations have been identified in ~15% of patients with familial isolated pituitary adenomas (FIPA). In addition, dysregulation of the cyclic adenosine monophosphate (cAMP) signalling pathway has been identified in both syndromic and sporadic somatotropinomas. While crosstalk between these two systems is known to occur, the exact mechanism of interaction remains elusive. The identification of direct binding...

Archipelago/hCdc4/Fbw7 is the F-box protein specific for recognising and binding phosphorylated cyclin E and targeting it for ubiquitination. Mutations in Archipelago that prevent it from binding to phoshorylated cyclin E have been described in various human cancers including breast, ovarian and endometrial tumours. Previous studies have suggested that cyclin E is over-expressed in corticotroph tumours and other pituitary adenoma subtypes, and we postulated that this may be se...

Introduction: Aryl hydrocarbon receptor interacting protein (AIP) is a multifunctional co-chaperone protein: it behaves as a tumour suppressor in the pituitary, but may have other roles including oncogenic function in other tissues. Protein phosphorylation is an important posttranslational modification that regulates protein activity, which is crucial for understanding protein function. To understand the molecular pathways altered in AIP deficient cells, we have performed glob...

Objectives: Somatotropinomas can be divided into three subgroups based on their distinct DNA methylation profiles1, one matching sparsely granulated (SG) and the other two matching densely granulated phenotypes (DG-A and DG-B). Sparsely granulated adenomas show fibrous body formation on cytokeratin immunohistochemistry, compared to diffuse staining in densely granulated adenomas. Methylation1 and gene expression data were analysed to identify (i) differen...

Background: Pituitary carcinoma is extremely rare and constitute only 0.1−0.2% of all pituitary tumors. Diagnosis is on evidence of metastasis, although these criteria has been challenged. Majority of pituitary carcinomas are functioning tumours, usually secreting ACTH (42%) or prolactin (33%). Common sites of metastasis include the brain, spinal cord, leptomeninges, bone, liver, lymph nodes and lung. Mean survival after detection of metastasis is around 1−2 years....

Introduction: Somatotroph adenomas are GH producing pituitary adenomas. There are two main types based on granulation pattern: sparsely and densely granulated. Each type also has their own fibrous body pattern. Sparsely granulated (SG) have a ‘dot-like’ fibrous body pattern and the densely granulated (DG) have a ‘perinuclear’ fibrous body pattern. The fibrous bodies are mainly composed of keratin 8. Previous microarray analysis revealed six differentially e...

Introduction: Around 15–20% of patients suffering from familial isolated pituitary adenoma (FIPA) possess heterozygous germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. AIP carriers are predisposed to pituitary adenomas with a penetrance of approximately 20%. No other tumours have been observed in subjects with AIP mutations, hence the name “isolated”. AIP is acting as a tumour suppressor gene in the p...

Introduction: Patients with aryl hydrocarbon receptor-interacting protein (AIP) gene mutations are predisposed to large, invasive, GH- or PRL-secreting pituitary tumours, occurring at a younger age and poorly responsive to treatment. The zebrafish (ZF) model provides anatomical and functional similarities to human neuroendocrine system.Methods: AIP knock down (KD) ZF embryos were generated using antisense morpholino oligonucleotides injected at one-cell ...

Introduction: Two childhood cases of somatotroph pituitary adenomas caused by aryl hydrocarbon receptor interacting protein (AIP) mutations highlight the importance of screening for familial isolated pituitary adenoma (FIPA) genes and wider family implications.Case 1: A 13.5-year-old girl presented with 5 years growth acceleration and size ten feet, with no headache or visual disturbance. Examination: coarse facial features, large hands and feet...