Endocrine Abstracts

The CaSR, a G-protein-coupled receptor that regulates extracellular calcium (Ca2+o), predominantly signals via G-protein-αq/11 (Gαq/11), initiating IP3-mediated intracellular calcium (Ca2+i) accumulation, and mitogen-activated protein kinase (MAPK) signalling. CaSR also activates MAPK signalling via Gαi/o, or by associating with the scaffolding protein β-arrestin. CaSR g...

Retrospective audit of Patients had Parathyroidectomy over 2 years in East Sussex NHS trust; 73 patients had Parathyroid surgery for Primary hyperparathyroidism during this period. We have collected the data using case notes and hospital electronic records. Fifty-six patients were females and 17 were Males. Ninety-three per cent of patients were more than 50 years old. Common presenting symptoms were Lethargy (51%), bone pain (44%) and other symptoms were polyuria, polydipsia....

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the combined occurrence of parathyroid tumours, and neuroendocrine tumours (NETs) of the pancreas and pituitary. Reliable biomarkers, ideally in plasma or serum, for the early detection and recurrence of MEN-1 associated tumours, and especially pancreatic NETs are required, and we explored the potential use of microRNAS (miRNAs), which are small non-coding RNAs that bind target mRNAs ...

Epigenetic modifications and chromatin remodelling have been demonstrated to play a key role in the development, and progression of multiple cancers, and compounds regulating these mechanisms represent a novel class of anti-cancer drugs. Menin, which is encoded by the MEN1 gene, whose mutations result in a syndrome characterised by pituitary, parathyroid and pancreatic islet tumours, binds histone modifying enzymes, including the histone methyltransferase MLL1. Furthe...

Idiopathic infantile hypercalcaemia (IHH) is an autosomal recessive disorder typically presenting in the first few months of life with failure to thrive, vomiting, dehydration, and nephrocalcinosis with hypercalcaemia and low or undetectable parathyroid hormone (PTH) concentrations. IHH is caused by loss-of-function mutations of the cytochrome P450 family 24 subfamily A member 1 (CYP24A1) gene that encodes the 514 amino acid protein 1,25-dihydroxyvitamin D3...

Introduction: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neuroendocrine tumors arising from chromaffin cells within adrenal medulla and autonomic paragranglia respectively. Recent evidences show that nearly one-third patients harbour germline mutation, namely in von Hippel-Lindau (VHL), REarranged during Transfection (RET), neurofibromatosis type 1 (NF 1) and succinate dehydrogenase (SDH) complex genes. However, the tumor morphology arising in various syndrom...

JQ1 is a bromodomain inhibitor that specifically targets the BET protein family (comprising Brd2, Brd3, Brd4 and BrdT), which promote the transcription of genes by binding acetylated histone residues and recruiting transcriptional machinery. JQ1 has been shown to have efficacy in the treatment of neuroendocrine tumours, however the genes regulated by the BET family in endocrine tissues, particularly in the pituitary, have not been elucidated. We therefore performed RNA-Seq ana...

Neuroendocrine tumours (NETs), occurring at multiple sites including the pancreas, lung and pituitary, are increasing in incidence and usually present at an advanced metastatic stage, and current medical treatments have limited efficacy. Epigenetic modifiers are promising new drugs, as mutations in the multiple endocrine neoplasia type 1 (MEN1) gene, encoding the histone methyltransferase MLL1 interacting protein, menin, are known to cause both familial and sporadic N...

There are currently no curative treatments for metastatic pancreatic neuroendocrine tumours (PNETs), and the 5-year survival is <50%. Such tumours frequently have mutations in chromatin remodelling genes as well as the protein encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, menin, which is mutated in up to 40% of sporadic PNETs, and binds the histone methyltransferase MLL1. Histone modifications, and specifically acetylated residues on histone tail...

Marshall-Smith syndrome (MSS) is a congenital disorder affecting skeletal and neural development due to mutations in the nuclear factor I/X (NFIX) gene. Of these mutations, 61% are small insertions/deletions, 12% are splice site mutations and 27% are large exonic deletions clustered in exons 6–10 of the NFIX gene. In order to derive a MSS mouse model, the N-ethyl-N-nitrosourea (ENU) mutagenesis DNA archive was screened ...