Endocrine Abstracts

Introduction: Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) predispose humans to pituitary adenomas, mostly GH and sometimes prolactin-secreting adenomas. Rodent models of heterozygous AIP loss provided mixed results, with little phenotype in heterozygote global knockouts to 80% in somatotroph-specific homozygote knockout animals. However, human patients with an AIP mutation often have mixed GH-PRL adenomas and, in a smaller pr...

Introduction: Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) predispose humans to pituitary adenomas, mostly GH and sometimes prolactin-secreting adenomas. Rodent models of heterozygous AIP loss provided mixed results, with little phenotype in heterozygote global knockouts to 80% in somatotroph-specific homozygote knockout animals. However, human patients with an AIP mutation often have mixed GH-PRL adenomas and, in a smaller pr...

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: 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...

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 ...

Introduction: Acromegaly links to cardiomyopathy and potential cardiac failure, if untreated. Mechanisms involved in acromegalic cardiomyopathy are incompletely understood. We investigated the effects of growth hormone (GH) excess and somatostatin receptor ligands (SRLs) on cardiac fibrosis using an acromegalic mouse model with pituitary-specific deletion of the Aip gene coding aryl hydrocarbon receptor interacting protein (AipFlox/Flox;Hesx1<su...

Introduction: Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene predispose to growth hormone (GH, 90% of patients) or prolactin (PRL)-secreting tumours, with negligible number of patients with other pituitary tumour types. Animal models of acromegaly are scarce and Aip models have controversial data. Therefore we have generated two pituitary-specific Aip knockout mouse models to study the consequences of loss of AIP p...