Endocrine Abstracts

G-protein coupled receptors (GPCR) mediate the effects of multiple hormones, and consequently are fundamental for endocrine functions including glucose homeostasis, thyroid function, fertility, control of urine output, and bone remodelling. Mutations in genes encoding GPCRs result in endocrine disorders, and studies of these mutations has improved understanding of GPCR signalling and trafficking pathways, and could facilitate novel therapies. The calcium-sensing receptor (CaSR...

G-protein coupled receptors (GPCR) mediate the effects of multiple hormones, and consequently are fundamental for endocrine functions including glucose homeostasis, thyroid function, fertility, control of urine output, and bone remodelling. Mutations in genes encoding GPCRs result in endocrine disorders, and studies of these mutations has improved understanding of GPCR signalling and trafficking pathways, and could facilitate novel therapies. The calcium-sensing receptor (CaSR...

It is an exciting time to be a basic scientist in endocrinology, with new technologies emerging, increasing opportunities to take advantage of large-scale genetic data, and innovative strategies to translate mechanistic insights into drug discovery and clinical practice. I will discuss what, in my opinion, are the most exciting basic research findings in endocrinology for this year....

This year marks 25 years since the calcium-sensing receptor (CaSR) was first identified in bovine parathyroid and the receptor has since emerged as a fundamental contributor to extracellular calcium (Ca2+e) homeostasis, by regulating parathyroid hormone release and urinary calcium excretion. The CaSR is a class C GPCR that is functionally active as a homodimer. It couples to multiple G-protein subtypes to activate intracellular calcium mobilisation and mi...

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, ...

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...

Vitamin D-dependent rickets type-1 (VDDR1) is an autosomal recessive disorder characterised by onset of rickets by 2 years of age, accompanied by poor growth and hypotonia, muscle weakness, seizures, hypocalcaemia with secondary hyperparathyroidism, hypophosphataemia and normal plasma 25-hydroxyvitamin D (25(OH2)D) concentration that distinguishes VDDR1 from vitamin D deficient rickets. VDDR1 is caused by loss-of-function mutations of the 25-hydroxyvitamin D 1-alpha...

The calcium-sensing receptor (CaSR), a class C G-protein coupled receptor (GPCR) is critical for calcium homeostasis. The presence of CaSR at the plasma membrane (PM) is regulated by a balance between internalisation via clathrin-mediated endocytosis, and agonist-induced PM insertion from intracellular receptor pools, in a mechanism known as agonist-driven insertional signalling. Recently, mutations of the clathrin-mediated endocytic adaptor protein-2 sigma subunit, AP2σ,...