title: Calcium-sensing receptor mediates Ca(2+) 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 Ca(2+) 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 Ca(2+) homeostasis by regulating synthesis of hypercalcemic (PTH1 and PTH2) and hypocalcemic (stanniocalcin [STC]) hormones. We report that PTH1, but not PTH2, increases Ca(2+) uptake through stimulation of the expression of the gene encoding the epithelial Ca(2+) channel (ecac). Furthermore, we demonstrate that CaSR, as a Ca(2+) sensor, may affect stc-1 and pth1 expressions differently, thereby suppressing ecac expression and Ca(2+) 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 Ca(2+) homeostasis in vertebrates.
authors.affiliation: Institute of Cellular and Organismic Biology (C.-H.L., C.-H.S., P.-P.H), Academia Sinica, Taipei 11529, Taiwan, Republic of China; and Institute of Fishery Science (C.-H.S., P.-P.H), National Taiwan University, Taipei 10617, Taiwan, Republic of China.
authors.forename: Chia-Hao
authors.initials: CH
authors.lastname: Lin
authors.forename: Che-Hsien
authors.initials: CH
authors.lastname: Su
authors.forename: Pung-Pung
authors.initials: PP
authors.lastname: Hwang
mesh_terms: D000818:Animals; D002116:Calcitonin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism*; D006706:Homeostasis; D006996:Hypocalcemia / Q000378:metabolism; D017403:In Situ Hybridization; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D010280:Parathyroid Glands / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D013696:Temperature; D019076:Transgenes; D015027:Zebrafish
chemical_list: D006023:Glycoproteins; D016376:Oligonucleotides, Antisense; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D044169:Receptors, Calcium-Sensing; C051795:teleocalcin; D002116:Calcitonin; D002118:Calcium