Endocrine Abstracts

Gastric inhibitory polypeptide (GIP) is a post-prandially secreted gut hormone that acts upon the GIP-receptor (GIPR), to stimulate insulin secretion. Animal studies indicate that GIP influences bone remodelling, and in humans, GIP administration decreases levels of bone resorption markers. However, the mechanisms by which GIP influences resorption remain to be elucidated. Therefore, we investigated how GIP (10nM) affects bone cell activity using primary human osteoclasts, hum...

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor (GPCR) that maintains systemic calcium homeostasis by detecting alterations in extracellular calcium, which it transduces into signalling changes, mainly via the Gq/11 pathway, leading to a decrease in PTH secretion. The importance of CaSR is highlighted by studies of patients that harbour germline CaSR mutations, which lead to a gain of receptor function in autosomal dominant...

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor (GPCR) that maintains systemic calcium homeostasis by detecting alterations in extracellular calcium, which it transduces into signalling changes, mainly via the Gq/11 pathway, leading to a decrease in PTH secretion. The importance of CaSR is highlighted by studies of patients that harbour germline CaSR mutations, which lead to a gain of receptor function in autosomal dominant...

Case history: Idiopathic Infantile Hypercalcaemia (IIH) classically presents in the first year of life, usually resolves by 1 year of age and is due to mutations in 1,25-dihydroxyvitamin D2 24-hydroxylase (CYP24A1) or, rarely, sodium-phosphate cotransporter-2A (SLC34A1). We report a case of IIH in a Caucasian female, who was born to non-consanguineous parents, with hypercalcaemia, hypercalciuria and associated complications persisting into adulthoo...

Loss- and gain-of-function mutations of the calcium-sensing receptor (CaSR) cause familial hypocalciuric hypercalcaemia (FHH) and autosomal dominant hypocalcaemia (ADH), respectively. The CaSR is a homodimeric receptor that has a 612 amino acid extracellular domain (ECD), which binds extracellular calcium (Ca2+e) and mediates dimer interactions upon ligand binding. The ECD consists of lobes 1 and 2, and a cysteine-rich domain (CRD). To elucidate the struc...

Loss- and gain-of-function mutations of the calcium-sensing receptor (CaSR) cause familial hypocalciuric hypercalcaemia (FHH) and autosomal dominant hypocalcaemia (ADH), respectively. The CaSR is a homodimeric receptor that has a 612 amino acid extracellular domain (ECD), which binds extracellular calcium (Ca2+e) and mediates dimer interactions upon ligand binding. The ECD consists of lobes 1 and 2, and a cysteine-rich domain (CRD). To elucidate the struc...

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...

Mutations of the calcium-sensing receptor (CaSR), G-protein alpha-11 subunit (Gα11), and adaptor protein-2 sigma subunit (AP2σ) resulting in a loss-of-function, cause familial hypocalciuric hypercalcemia types 1-3 (FHH1-3), respectively. We investigated a family with FHH (four affected and two unaffected members) for CaSR, Gα11 and AP2σ mutations, and identified a heterozygous Gα11 missense mutation, Phe220Ser, which is predicted to disrupt a cluster o...

Whole genome sequencing (WGS) has the potential to identify nearly all forms of genetic variation. In complex disorders with multiple manifestations WGS can establish a definitive diagnosis that may change clinical management (Stavropoulos et al. 2016 Genomic Med). Here, we report on the utility of WGS in establishing the correct diagnosis in a family with hyperuricaemia. Hyperuricaemia may occur as: part of a syndromic disorder (e.g. Lowe syndrome, renal col...