Endocrine Abstracts

Aryl hydrocarbon receptor-interacting protein (AIP) is a highly expressed, evolutionary conserved little-known co-chaperone molecule that can bind to client proteins. Heterozygous loss-of-function mutations of AIP are associated with pituitary adenomas. Multiple lines of evidence suggest that AIP has important functions beyond the pituitary gland. Homozygous loss of AIP is lethal, with cardiac abnormalities seen in mice and failure-to-thrive seen in fruit flies and C.elegans. ...

Background: No predictive biomarkers for NFPT recurrence have been identified, apart from Ki67. We employed high-throughput mass spectrometry-based analyses to examine the phosphorylation pattern of different subsets of NFPTs. Methods: Based on histopathological, radiological and surgical features, NFPTs were sub-grouped into three groups: non-invasive (n = 15), invasive (n = 10) and recurrent (n = 5) subtypes. Invasiveness was...

Introduction: Patients with a germline loss-of-function mutation in AIP are predisposed to young-onset GH excess resulting in gigantism or acromegaly. Acromegaly leads to disease-specific cardiomyopathy with biventricular hypertrophy and diastolic dysfunction progressing to fulminant cardiac failure if left untreated, therefore it is vital to have a tractable animal model to investigate the diseaseFindings: Our AipFlox/Flox;<...

Introduction: Hormone macromolecules are complexes of hormones with other compounds, most often with IgG immunoglobulin. They show variable immunoreactivity in immunochemical tests (IRMA, ELISA, CLIA, ECLIA) and usually have a weak biological effect. They can interfere with immunological assays of various hormones. Some known hormone macrocomplexes are: BB-PRL (24% - 34%), macro-TSH (0.6% - 1.2%) and very rare macromolecules of various hormones: calcitonin, PTH, insulin (singl...

Introduction: The tumour microenvironment significantly influences tumour behaviour. Little is known about the pituitary adenoma microenvironment. AIP mutation positive (AIPpos) patients develop often aggressively growing pituitary tumours and the study of their microenvironment might identify factors leading to this aggressive phenotype which could help predict tumour behaviour and identify novel therapeutic targets.</p...

Introduction: The tumour microenvironment significantly influences tumour behaviour. Little is known about the pituitary adenoma microenvironment. AIP mutation positive (AIPpos) patients develop often aggressively growing pituitary tumours and the study of their microenvironment might identify factors leading to this aggressive phenotype which could help predict tumour behaviour and identify novel therapeutic targets.</p...

Background: No predictive biomarkers have been identified for clinically nonfunctioning pituitary tumour (NFPT) recurrence, with Ki67 being controversial. We employed quantitative mass spectrometry-based analyses to examine the differential expression of proteins in NFPTs.Methods: NFPTs were sub-grouped: non-invasive/non-recurrent group (NI/NR-G, n=5), invasive group (I-G, n=10) and recurrent group (R-G, n=5). Invasiveness was ...

Background: The cyclic GMP-AMP synthase stimulator of interferon genes (cGAS-STING) signalling pathway is an element of the innate immune response and is activated by the presence of DNA in the cytosol. Triggering of this immune response may occur in the setting of infection or neoplasia. Activation of this pathway results in phosphorylation of interferon regulatory factor 3 and downstream transcription of cytokines such as interferon β and interleukin-6. Polyinosinic:pol...

Introduction: Pachydermoperiostosis (primary hypertrophic osteoarthropathy, PHOA) is a rare genetic condition characterised by digital clubbing, pachydermia, hyperhidrosis, cutis verticis gyrata and periostosis. The SLCO2A1 transporter and HPGD enzyme genes play an important role in prostaglandin metabolism, hence loss of function mutations in them causes PHOA. To date, according to the VarSome database 101 and 41 variants have been identified in the SLCO...

Introduction: AIP mutations are responsible for 15-30% of cases of familial isolated pituitary adenomas. The pathophysiology that drives this AIP-related pituitary tumorigenesis is not fully understood. We developed a pituitary-specific Aip knockout (KO) mouse model, which mostly recapitulates the human phenotype.Aims: To performed comparative gene expression analysis of Aip-KO mouse pituitary tumours and AIP mutation positive ...