Regulation of murine fetal-placental calcium metabolism by the calcium-sensing receptor.
Regulation of murine fetal-placental calcium metabolism by the calcium-sensing receptor.
复制标题
钙敏感受体对小鼠胎儿胎盘钙代谢的调节。
DOI：
10.1172/jci2940
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Kronenberg,HM
中科院分区：
文献类型：
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作者：
Kovacs,CS;Ho-Pao,CL;Hunzelman,JL;Lanske,B;Fox,J;Seidman,JG;Seidman,CE;Kronenberg,HM
在成人中，钙感应受体（CaSR）通过调节甲状旁腺激素的分泌来控制细胞外钙浓度，但其在胎儿生命中的作用尚不清楚。我们使用CaSR基因敲除小鼠来研究CaSR在调节胎儿钙代谢中的作用。胎儿血液中正常钙浓度高于母体水平，其升高取决于甲状旁腺素相关肽（PTHrP）。杂合子（+/-）和纯合子（-/-）CaSR破坏导致胎儿钙水平进一步升高。这种增加被PTHrP基因的同时破坏略微减弱，并被PTH/ PTHrP受体基因的破坏完全逆转。血清甲状旁腺激素和1,25 -二羟基维生素D水平明显高于正常的低胎儿水平。CaSR-/-胎儿羊水（尿）中游离脱氧吡啶水平升高；结果提示胎儿骨吸收增加。由于CaSR的破坏，胎盘钙转移减少，肾钙排泄增加。这些研究表明，在正常升高（和pthrp依赖）的胎儿钙水平存在下，CaSR正常抑制PTH分泌。CaSR的破坏导致胎儿甲状旁腺功能亢进和高钙血症，并对胎盘钙转移产生额外影响。
The calcium-sensing receptor (CaSR) regulates PTH secretion to control the extracellular calcium concentration in adults, but its role in fetal life is unknown. We used CaSR gene knockout mice to investigate the role of the CaSR in regulating fetal calcium metabolism. The normal calcium concentration in fetal blood is raised above the maternal level, an increase that depends upon PTH-related peptide (PTHrP). Heterozygous (+/-) and homozygous (-/-) disruption of the CaSR caused a further increase in the fetal calcium level. This increase was modestly blunted by concomitant disruption of the PTHrP gene and completely reversed by disruption of the PTH/ PTHrP receptor gene. Serum levels of PTH and 1, 25-dihydroxyvitamin D were substantially increased above the normal low fetal levels by disruption of the CaSR. The free deoxypyridinoline level was increased in the amniotic fluid (urine) of CaSR-/- fetuses; this result suggests that fetal bone resorption is increased. Placental calcium transfer was reduced, and renal calcium excretion was increased, by disruption of the CaSR. These studies indicate that the CaSR normally suppresses PTH secretion in the presence of the normal raised (and PTHrP-dependent) fetal calcium level. Disruption of the CaSR causes fetal hyperparathyroidism and hypercalcemia, with additional effects on placental calcium transfer.