Increased intestinal chromatin template activity. Influence of 1alpha,25-dihydroxyvitamin D3 and hormone-receptor complexes.
Increased intestinal chromatin template activity. Influence of 1alpha,25-dihydroxyvitamin D3 and hormone-receptor complexes.
复制标题
肠道染色质模板活性增加。
DOI：
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发表时间：
1976
影响因子：
4.8
通讯作者：
M. Haussler
中科院分区：
文献类型：
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作者：
J. Zerwekh;T. J. Lindell;M. Haussler
1 α，25-二羟基维生素D3对幼雏肠道靶组织染色质模板活性的影响，采用体外大肠杆菌RNA聚合酶检测。给药2小时后，模板容量的最大刺激值为对照值的12 ~ 20%。这种快速效应先于肠道对1 α，25-二羟基维生素D3的生物反应，而在肝脏或肾脏等其他组织中未观察到。肠道染色质模板活性的体内增强是针对1 α，25-二羟维生素D3激素的，因为同等剂量的25-羟维生素D3或维生素D3在2至3小时内不会引起反应。只有1 α -羟维生素D3，一种合成的甾醇，可以迅速代谢为1 α - 25-二羟维生素D3，能够在体内分解天然激素。为了进一步阐明1α，25-二羟基维生素D3的核作用机制，我们将该激素与肠细胞质在0度下预孵育，形成激素受体复合物。将激素受体复合物添加到纯化的肠粘膜核中并在25度下孵育1小时后，与不含激素的类似体外孵育法制备的染色质相比，从该重组体系中分离出的染色质显示出显著的模板活性增加。这种刺激比对照值高12 - 24%，表现出对肠细胞胞浆的绝对需求。这种反应对生理水平的1 α，25-二羟维生素D3有特异性，但对25-羟维生素D3的药理学剂量也有特异性。由此可见，1 α，25-二羟基维生素D3对肠道靶组织染色质模板活性的刺激可能是钙转运增强的最终生理反应的一个组成部分。
1alpha,25-Dihydroxyvitamin D3 administration to rachitic chicks results in an increase in the chromatin template activity of intestinal target tissue assayed in vitro using Escherichia coli RNA polymerase. The maximum stimulation of template capacity was 12 to 20% over control values and occurred 2 hours after administration of the sterol. This rapid effect preceded the biologic response to 1alpha,25-dihydroxyvitamin D3 in the intestine and was not observed in other tissues such as liver or kidney. The in vivo enhancement of intestinal chromatin template activity was specific for the 1alpha,25-dihydroxyvitamin D3 hormone in that equivalent doses of 25-hydroxyvitamin D3 or vitamin D3 did not elicit a response in 2 to 3 hours. Only 1alpha-hydroxyvitamin D3, a synthetic sterol which is very rapidly metabolized to the 1alpha,25-dihydroxyvitamin D3 form, was able to minic the natural hormone in vivo. To further elucidate the nuclear mechanism of action of 1alpha,25-dihydroxyvitamin D3, the hormone was preincubated at 0 degrees with intestinal cytosol to form hormone-receptor complexes. After addition of the hormone-receptor complexes to purified intestinal mucosa nuclei and incubation for 1 hour at 25 degrees, chromatin isolated from this reconstituted system displayed a significant increase in template activity as compared to chromatin prepared from similar in vitro incubations not containing hormone. This stimulation was 12 to 24% over control values and exhibited an absolute requirement for intestinal cell cytosol. The response was specific for physiologic levels of 1alpha,25-dihydroxyvitamin D3, but occurred with pharmacologic doses of 25-hydroxyvitamin D3. It is concluded that a stimulation of the chromatin template activity of intestinal target tissue by 1alpha,25-dihydroxyvitamin D3 may be an integral part of the ultimate physiologic response of enhanced calcium transport.