Endocrine Abstracts

G-protein coupled receptors (GPCRs) comprise the largest superfamily within the human proteome, and are frequent targets for hormones and drugs. Important insights about the roles of GPCRs in endocrinology have been provided by studies of clinical disorders, as illustrated by those of calcium regulation, which involves the parathyroids, first discovered in an Indian Rhinoceros by Sir Richard Owen in 1849. The parathyroids and kidneys express the extracellular calcium-sensing r...

Funding and publication in biomedical research has become highly competitive and to succeed, it has become increasingly important to include statements that have broad appeal, i.e., impact, especially in the summaries of grant applications and manuscripts. The key elements in these statements are to keep them short, simple and ‘sweet’ (i.e. appealing to a wider audience). Consider the three following statements:i) We’ve got no money, so we...

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumours. In addition, some patients may also develop adrenal cortical tumours, carcinoid, facial angiofibromas, collagenomas, and lipomatous tumours. The gene causing MEN1 is located on chromosome 11q13, and encodes a 610 amino-acid protein, menin, that represents a tumour suppressor, as its loss of expression is ...

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease characterised by the combined occurrence of parathyroid, pancreatic islet and anterior pituitary tumours. Over 60% of the anterior pituitary tumours in MEN1 patients are prolactinomas, ~25% are somatotrophinomas, ~5% are corticotrophinomas, and the remainder appear to be non-functioning. The MEN1 gene, a tumour suppressor, is located on chromosome 11q13, and more than 1300 MEN1 mutations, which are lik...

Rajesh Thakker is the May Professor of Medicine at the University of Oxford, UK. He received his medical degree from the University of Cambridge in 1980, and from 1981 to 1988 he undertook postgraduate clinical and research training at The Middlesex Hospital, The Hammersmith (Royal Postgraduate Medical School, RPMS), Hospital, and Northwick Park (MRC Clinical Research Centre) Hospital (London). In 1988, he was appoint...

A 35-year-old patient was referred to a tertiary referral unit for further investigation of severe watery diarrhea. Infectious agents had already been excluded. Biochemistry revealed a strikingly raised serum calcium concentration of 4.09 mmol/l (NR 2.1–2.65 mmol/l), chromogranin A was grossly elevated at 293 U/l (NR 2–18 U/l) and vasoactive intestinal peptide (VIP) was also raised at 130 pg/ml (NR 10–60 pg/ml). Computed tomography (CT) of the abdomen demonstrat...

The prolactin receptor (PRLR) signals predominantly through the JAK2-STAT5 pathway regulating multiple physiological functions relating to fertility, lactation, and metabolism. Understanding of PRLR signalling is incompletely defined, with progress hampered by a lack of reported disease-associated variants in the genes for the prolactin hormone (PRL) and/or PRLR. To date, two common germline PRLR variants are reported to demonstrate constitutive activity, with one, Ile146Leu, ...

Mutations of the cell division cycle 73 (CDC73) gene, which encodes the 531 amino acid protein parafibromin, are associated with the Hyperparathyroidism-Jaw Tumour (HPT-JT) syndrome, an autosomal dominant disorder characterised by parathyroid tumours and ossifying jaw fibromas. In addition, ∼75% of women with HPT-JT develop benign and malignant uterine tumours, which include endometrial hyperplasia, adenosarcomas, adenofibromas, and leiomyomas. To explore the role of <em...

Investigation of parathyroids in mouse models is hampered by difficulties in identifying the small glands. We developed a microsurgical technique to identify murine parathyroids by dissecting from the distal thyrothymic ligament to the lower thyroid pole (LTP). Parathyroids were identified in 100 mice which comprised: 48 mice deleted for a cell-division-cycle 73 gene allele (Cdc73+/−), involved in the hyperparathyroidism-jaw tumour syndrome; ...

The Multiple Endocrine Neoplasia type 1 (MEN1) gene is located on chromosome 11q13 and patients with mutations develop parathyroid, pancreatic and pituitary tumours. MEN1 mutations also cause familial isolated primary hyperparathyroidism (FIHP) and the same MEN1 mutations, in different families, can cause either FIHP or MEN1. This emphasises the importance of genetic background in altering the expression of a mutation, and suggests the presence of genetic ...