Parathyroid Hormone - Regulation of PTH Secretion

Regulation of PTH Secretion

Secretion of parathyroid hormone is controlled chiefly by serum through negative feedback. Calcium-sensing receptors located on parathyroid cells are activated when is low. The G-protein coupled calcium receptors (CaR) sense extracellular calcium and may be found on the surface on a wide variety cells distributed in the brain, heart, skin, stomach, C cells, and other tissues. In the parathyroid gland, sensation of high concentrations of extracellular calcium result in activation of the Gq G-protein coupled cascade through the action of phospholipase C. This hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to liberate intracellular messengers IP3 and diacylglycerol (DAG). Ultimately, these two messengers result in a release of calcium from intracellular stores and a subsequent flux of extracellular calcium into the cytoplasmic space. The effect of this signaling of high extracellular calcium results in an intracellular calcium concentration that inhibits the secretion of preformed PTH from storage granules in the parathyroid gland. In contrast to the mechanism that most secretory cells use, calcium inhibits vesicle fusion and release of PTH. In the parathyroids, magnesium serves this role in stimulus-secretion coupling. Hypomagnesia may result in a paralysis of PTH secretion and lead to a form of hypoparathyroidism that is reversible. Hypermagnesemia also results in inhibition of PTH secretion.