PTH(7-84) inhibits PTH(1-34)-induced 1,25-(OH)2D3 production in murine renal tubules.
PTH(7-84) inhibits PTH(1-34)-induced 1,25-(OH)2D3 production in murine renal tubules.
复制标题
DOI：
10.1016/j.bbrc.2009.02.023
复制
发表时间：
2009-04
影响因子：
3.1
通讯作者：
K. Nakajima;K. Nohtomi;Masayo Sato;K. Takano;Kanji Sato
中科院分区：
文献类型：
--
作者：
K. Nakajima;K. Nohtomi;Masayo Sato;K. Takano;Kanji Sato
为了阐明 PTH(1-84) 的降解产物 PTH(7-84) 抑制 PTH(1-84) 诱导的骨吸收是否也对肾脏产生拮抗作用，我们研究了 PTH(7-84) 对原代培养的小鼠肾小管中 PTH(1-34) 诱导的 1,25-(OH)2D3 产生的影响。在无血清MEM中培养7天的新生小鼠肾小管用PTH(1-34)和/或PTH(7-84)处理。添加 25-OHD3(10−6M) 3 小时后，测定 1,25-(OH)2D3。 PTH(1-34) 刺激 25-OHD3 转化为 1,25-(OH)2D3，而 PTH(7-84) 剂量依赖性地抑制这一过程。实时PCR显示PTH(1-34)增加1α-羟化酶mRNA的表达水平，而PTH(7-84)不影响1α或24-羟化酶mRNA的表达水平。这些体外数据表明，PTH(7-84) 通过不同于 I 型 PTH/PTHrP 受体的受体在肾小管中引发拮抗作用。这可能至少部分解释了患有严重原发性甲状旁腺功能亢进症并肾衰竭的患者血清 1,25-(OH)2D 水平降低的原因。
To elucidate whether PTH(7-84), a degradation product of PTH(1-84), which inhibits PTH(1-84)-induced bone resorption, also exerts an antagonistic effect on the kidney, we studied the effect of PTH(7-84) on PTH(1-34)-induced production of 1,25-(OH)2D3in primary cultured murine renal tubules. Neonatal mouse renal tubules cultured in serum-free MEM for 7days were treated with PTH(1-34) and/or PTH(7-84). Three hours after addition of 25-OHD3(10−6M), 1,25-(OH)2D3was determined. PTH(1-34) stimulated the conversion of 25-OHD3to 1,25-(OH)2D3, and PTH(7-84) dose-dependently inhibited this process. Real-time PCR revealed that PTH(1-34) increased the expression level of 1α-hydroxylase mRNA, whereas PTH(7-84) did not affect the expression level 1α or 24-hydroxylase mRNA. These in vitro data suggest that PTH(7-84) elicits an antagonistic effect in renal tubules through receptors different from the type I PTH/PTHrP receptor. This may at least partly account for the decreased serum level of 1,25-(OH)2D in patients with severe primary hyperparathyroidism with renal failure.