The calcium-sensing receptor (CaSR) is a class C G-protein-coupled receptor (GPCR) that plays a fundamental role in extracellular calcium homeostasis by regulating parathyroid hormone (PTH) release. Although the CaSR was identified over 25 years ...

The extracellular Ca 2+ -sensing receptor (CaSR) plays a nonredundant role in the functions of the parathyroid gland (PTG) and the kidney. Severe hyperparathyroidism, premature death, and incomplete gene excision in Casr−/− mice have precluded the …

We studied mice with or without heterozygous deletion of the Casr in the parathyroid gland (PTG) [ (PTG) CaSR (+/-)] to delineate effects of age and sex on manifestations of hyperparathyroidism (HPT). In control mice, aging induced a left-shift in the Ca (2+) /parathyroid hormone (PTH) set point accomp …

A mechanistic model of PTG biology takes the signaling of the CaSR and VDR and the influence of critical parameters on the receptors into account. Thereby, the adaptation of PTH synthesis rate, intracellular degradation rate, and PTG cell proliferation rate can be properly accounted for.

2018年4月4日 · We generated mouse strains with PTG-specific deletion of Klotho and CaSR and dual deletion of both genes. We show that ablating CaSR in the PTGs increases PTH synthesis, that Klotho has a pivotal role in suppressing PTH in the absence of CaSR, and that CaSR together with Klotho regulates PTH biosynthesis and PTG growth.

Elevations outside the normal range activate the CaSR on the PTG leading to suppression of PTH. In the FGF23–klotho axis (effects shown in green), FGF23 is produced by bone and binds to FGF receptor–klotho, which reduces PTH secretion and plasma membrane expression of sodium–phosphate transporters (NPT) at the renal proximal tubule.

2020年6月9日 · Results: PTG CaSR expression significantly decreased in the presence of a severe CKD environment, even without the high phosphate load. Ki67 expressing cells in PTGs were significantly higher only in the CKD rats fed a high phosphorus diet.

To determine definitively the role of CaSRs in skeletal development, we generated conditional knockouts of Casr in parathyroid, bone, and cartilage cells. Our findings support a requirement for the CaSR in bone growth and mineralization by modulating functions of …

We first studied heterozygous PTG-specific Casr knockout [ PTG CaSR (+/−) or Het-KO] mice and control littermates [CaSR flox/flox and/or PTH Cre (+/−)] to determine the impact of sex and age on levels of serum intact PTH (sPTH), total calcium …

According to a recent study, loss of CaSR in PTG causes serum PTH rise and PTG hyperplasia, which is exacerbated by additional deletion of Klotho in PTG. This shows that Klotho plays a vital function in suppressing the generation of PTH and the development of PTG in the lack of CaSR.