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: 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...

Germline mutations in BRAF and other components of the RAS/MAPK pathway are found in RASopathies, whose features include short stature and pubertal delay. The underlying mechanism of endocrinopathies in RASopathies has not been fully elucidated. We report four BRAF mutations (two of which are novel) in four children with congenital hypopituitarism and RASopathy features. To demonstrate the functional role of the variants we performed phosphoproteomic analyses...