Sensing Calcium Levels: The Biology of the Parathyroid Cells

Abstract The parathyroid glands play a pivotal role in orchestrating mineral metabolism and maintaining serum calcium and phosphate levels within a narrow range. These ions themselves, together with other hormones classically implicated in their fine tuning, are able to regulate parathyroid function, establishing feedback mechanisms, which modulate parathyroid hormone (PTH) secretion. Calcium ions activate the calcium sensing receptor (CaSR) expressed on the parathyroid cell, triggering intracellular signaling able to inhibit PTH secretion. In conditions of hypocalcemia, these pathways are turned off and PTH is promptly released from the parathyroids. Recent findings have demonstrated that PTH secretion is a mechanism dependent on endonuclease Dicer and miRNA maturation. Although a specific phosphate sensor has yet to be identified, phosphate is also sensed by the parathyroids cells. High extracellular phosphate levels increase serum PTH levels, stabilizing PTH mRNA. Signals eliciting PTH synthesis and secretion are also able to induce parathyroid hyperplasia in the long term, inducing cell proliferation. A parathyroid cell culture model is needed to better dissect the mechanisms controlling PTH transcription and secretion and to test new compounds able to modulate the different intracellular signaling pathways.