Calcium-Sensing receptor mediates Ca2+ homeostasis by modulating expression of PTH and stanniocalcin

Abstract

Regulation of the synthesis and/or secretion of hypocalcemic and hypercalcemic hormones by the calcium-sensing receptor (CaSR) is believed to be a major pathway for maintaining Ca2+ homeostasis in vertebrates, based primarily on findings in mammals. However, understanding the evolution of this physiological process requires that it be described in nonmammalian species. Here, we describe the use of zebrafish as a model to investigate whether CaSR contributes to body fluid Ca2+ homeostasis by regulating synthesis of hypercalcemic (PTH1 and PTH2) and hypocalcemic (stanniocalcin [STC]) hormones.Wereport that PTH1, but not PTH2, increases Ca2+ uptake through stimulation of the expression of the gene encoding the epithelial Ca2+ channel (ecac). Furthermore, we demonstrate that CaSR, as a Ca2+ sensor, may affect stc-1 and pth1 expressions differently, thereby suppressing ecac expression and Ca2+ uptake. Finally, we show that CaSR knockdown has time-dependent effects on STC-1 and PTH1 expression, and these 2 hormones have mutual effects on the expression, thus forming a possible counterbalance. These findings enhance our understanding of CaSR-PTH-STC control of Ca2+ homeostasis in vertebrates. Copyright © 2014 by The Endocrine Society.