Endocrine Abstracts

The onset of lactation after childbirth is a key determinant of successful breastfeeding. Copious milk secretion occurs by postpartum day 4 and is mediated by a decline in serum progesterone and high serum prolactin. However, the threshold prolactin concentration required is unclear. It is also unknown if changes in mammary prolactin sensitivity contribute to the initiation of lactation. To investigate this, we recruited 52 healthy pregnant women aged 26-42 years following inf...

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...

Familial hypocalciuric hypercalcaemia (FHH) is an inherited disorder of calcium homeostasis, which is caused by germline loss-of-function mutations of the calcium-sensing receptor (CaSR) in ˜70% of cases. We report a 22 year old woman who was referred with asymptomatic hypercalcaemia. Biochemical investigations revealed hypercalcaemia on 3 of 4 occasions with adjusted serum calcium ranging from 2.59–2.80 mmol/l (normal range 2.20–2.60 mmol/l). Parathyroid hormon...

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor that regulates extracellular calcium concentration. The CaSR is also implicated in the pathogenesis of non-calcium disorders such as vascular calcification and diabetes, which are leading causes of cardiovascular disease. Common CaSR single nucleotide polymorphisms (SNPs) have been demonstrated to be determinants of calcium metabolism. The aim of this study was to investigate whether CaSR SNPs may influence va...

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...

The modulation of pancreatic islet mass represents a novel therapeutic approach for the management of diabetes mellitus. G-protein coupled receptors (GPCRs) regulate beta-cell expansion and proliferation, and the objective of this study was to assess whether the calcium-sensing receptor (CaSR), which is an abundantly expressed beta-cell GPCR, may influence islet mass and systemic glucose homeostasis, and thus represent an exploitable drug target in some forms of diabetes. We c...

Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder characterized by lifelong elevation of serum calcium concentrations with inappropriately low urinary calcium excretion. Three types referred to as FHH1, FHH2 and FHH3 and located on chromosomes 3q21.1, 19p and 19q13.3, respectively, have been reported. FHH1, caused by loss-of-function mutations of the calcium-sensing receptor (CaSR), accounts for >65% of FHH patients. To identify the gen...

Familial hypocalciuric hypercalcaemia types 1, 2, and 3 (FHH1, FHH2, and FHH3) are caused by loss-of-function mutations of the calcium-sensing receptor (CaSR), G-protein subunit α11 (Gα11) and adaptor protein 2 sigma subunit (AP2σ), respectively; whilst autosomal dominant hypocalcaemia types 1 and 2 (ADH1 and ADH2) are due to gain-of-function mutations of CaSR and Gα11, respectively. We therefore hypothesised that gain-of-function AP2σ mutations may re...

Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder characterized by hypercalcaemia and inappropriately low urinary calcium excretion, and is occasionally associated with acute pancreatitis. FHH can be classified into three types: FHH type 1, caused by loss-of-function mutations of the calcium-sensing receptor (CaSR), which accounts for >65% of cases; FHH type 2, due to loss-of-function mutations of the G-protein α 11 subunit (Gα11), of ...