Regulation by vitamin D metabolites of messenger ribonucleic acid for preproparathyroid hormone in isolated bovine parathyroid cells.

Regulation by vitamin D metabolites of messenger ribonucleic acid for preproparathyroid hormone in isolated bovine parathyroid cells.
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维生素 D 代谢物对离体牛甲状旁腺细胞中前甲状旁腺激素前甲状旁腺激素的信使核糖核酸的调节。

DOI:
10.1073/pnas.82.12.4270
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发表时间:
1985
影响因子:
11.1
通讯作者:
Sherwood,LM
Sherwood,LM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Silver,J;Russell,J;Sherwood,LM

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我们最近已经确定,高钙浓度,在平行的甲状旁腺激素(PTH)分泌的抑制作用,可逆地和特异性地减少preproPTH mRNA在培养的牛甲状旁腺细胞。为了确定维生素D代谢产物是否也调节preproPTH mRNA的含量,我们在相同的培养系统中测试了它们对牛甲状旁腺细胞的影响。通过斑点杂交或用标记的克隆cDNA探针的印迹杂交测定preproPTH mRNA的水平。孵育与1,25-dihydroxycholecalciferol在不同的剂量从10 pM到0.1 μ M引起mRNA直接下降到50%的控制值在48 hr. There是没有证据表明,1,25-dihydroxycholecalciferol,即使在最高浓度,有任何毒性作用的细胞数量或活力或总RNA或RNA合成。在相同的实验中,α-肌动蛋白mRNA的水平没有变化,并且preproPTH mRNA的抑制是可逆的。当评价各种维生素D代谢物抑制preproPTH mRNA的相对效力时,1,25-二羟基胆钙化醇大于24,25-二羟基胆钙化醇大于25-羟基胆钙化醇大于维生素D3(胆钙化醇)。这些作用是高度特异性的,表明维生素D代谢产物在调节PTH的产生中起重要作用。
We have recently determined that high calcium concentrations, in parallel with their suppressive effects on parathyroid hormone (PTH) secretion, reversibly and specifically decrease preproPTH mRNA in cultured bovine parathyroid cells. In order to determine whether vitamin D metabolites also regulate the content of preproPTH mRNA, we tested their effects on bovine parathyroid cells in the same culture system. Levels of preproPTH mRNA were determined by dot-blot hybridization or blot hybridization with a labeled cloned cDNA probe. Incubation with 1,25-dihydroxycholecalciferol at doses varying from 10 pM to 0.1 microM caused a direct decrease in mRNA down to 50% of control values at 48 hr. There was no evidence that 1,25-dihydroxycholecalciferol, even at the highest concentrations, had any toxic effects on cell number or viability or on total RNA or RNA synthesis. Levels of alpha-actin mRNA did not change in the same experiments, and the suppression of preproPTH mRNA was reversible. When the relative potency of various vitamin D metabolites in suppressing preproPTH mRNA was evaluated, 1,25-dihydroxycholecalciferol greater than 24,25-dihydroxycholecalciferol greater than 25-hydroxycholecalciferol greater than vitamin D3 (cholecalciferol). These effects were highly specific and suggest that vitamin D metabolites play an important role in regulating the production of PTH.