Vitamin D3, lactose, and xylitol stimulate chromaffin cell proliferation in the rat adrenal medulla.
Vitamin D3, lactose, and xylitol stimulate chromaffin cell proliferation in the rat adrenal medulla.
复制标题
维生素 D3、乳糖和木糖醇刺激大鼠肾上腺髓质中的嗜铬细胞增殖。
DOI：
10.1006/taap.1996.0204
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
McClain,RM
中科院分区：
文献类型：
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作者：
Tischler,AS;Powers,JF;Downing,JC;Riseberg,JC;Shahsavari,M;Ziar,J;McClain,RM
大鼠长期食用富含糖或糖醇的食物会导致嗜铬细胞瘤的发病率增加。这种关系被假设是基于肠道Ca2+吸收增加导致的Ca2+稳态改变。在长期毒性研究中，与大鼠嗜铬细胞瘤相关的其他药物已被证明可增加嗜铬细胞增殖，从而提示肿瘤继发于嗜铬细胞更新增加。我们已经证明了维生素D3对染色质细胞增殖的显著刺激，这是一种对Ca2+吸收的有力刺激，以前与肾上腺髓质毒性无关。这种效果在膳食补充的第一周可以检测到，并持续4周。乳糖和木糖醇是与嗜铬细胞瘤相关的糖和糖醇的代表，它们也具有有丝分裂作用，但程度较轻，在第4周的膳食补充中首次检测到它们的影响。维生素D3及其活性代谢物骨化三醇、乳糖和木糖醇在体外均不能刺激大鼠染色质细胞的增殖。这些药物的有丝分裂作用可能是在突触前介导的。这些数据表明，Ca2+稳态的改变可能会增加嗜铬细胞的增殖，并支持含有高浓度糖和糖醇的饮食通过这种机制继发引起大鼠嗜铬细胞瘤的假设。
Chronic consumption by rats of diets rich in sugars or sugar alcohols leads to an increased incidence of pheochromocytomas. This relationship is hypothesized to be based on altered Ca2+homeostasis due to increased intestinal Ca2+absorption. Other agents associated with pheochromocytomas in rats in long-term toxicity studies have been shown to increase chromaffin cell proliferation, leading to the suggestion that the tumors occur secondarily to increased chromaffin cell turnover. We have demonstrated marked stimulation of chromaffin cell proliferation by vitamin D3, a potent stimulus to Ca2+absorption not previously associated with adrenal medullary toxicity. This effect is detectable during the first week of dietary supplementation and persists throughout a 4-week time course. Lactose and xylitol, representative of sugars and sugar alcohols associated with pheochromocytomas, are also mitogenic but to a lesser extent, with their effects first detectable during Week 4 of dietary supplementation. Vitamin D3, its active metabolite calcitriol, lactose, and xylitol all fail to stimulate proliferation of rat chromaffin cellsin vitro.The mitogenic effects of these agents may be mediated presynapticallyin vivo.The data suggest that altered Ca2+homeostasis may increase chromaffin cell proliferation and support the hypothesis that diets containing high concentrations of sugars and sugar alcohols cause pheochromocytomas in rats secondarily by this mechanism.