Fernandes I, Hampson G, Cahours X, Morin P, Coureau C, Couette S, Prie D, Biber J, Murer H, Friedlander G, Silve C
Inserm U 426, Faculté Xavier Bichat and Université Paris VII, France.
J Clin Invest. 1997 Nov 1;100(9):2196-203. doi: 10.1172/JCI119756.
To explore the possibility that vitamin D status regulates sulfate homeostasis, plasma sulfate levels, renal sulfate excretion, and the expression of the renal Na-SO4 cotransporter were evaluated in vitamin D-deficient (D-D-) rats and in D-D- rats rendered normocalcemic by either vitamin D or calcium/lactose supplementation. D-D- rats had significantly lower plasma sulfate levels than control animals (0.93+/-0.01 and 1.15+/-0.05 mM, respectively, P < 0.05), and fractional sulfate renal excretion was approximately threefold higher comparing D-D- and control rats. A decrease in renal cortical brush border membrane Na-SO4 cotransport activity, associated with a parallel decrease in both renal Na-SO4 cotransport protein and mRNA content (78+/-3 and 73+/-3% decreases, respectively, compared with control values), was also observed in D-D- rats. Vitamin D supplementation resulted in a return to normal of plasma sulfate, fractional sulfate excretion, and both renal Na-SO4 cotransport mRNA and protein. In contrast, renal sulfate excretion and renal Na-SO4 cotransport activity, protein abundance, and mRNA remained decreased in vitamin D-depleted rats fed a diet supplemented with lactose and calcium, despite that these rats were normocalcemic, and had significantly lower levels of parathyroid hormone and 25(OH)- and 1,25(OH)2-vitamin D levels than the vitamin D-supplemented groups. These results demonstrate that vitamin D modulates renal Na-SO4 sulfate cotransport and sulfate homeostasis. The ability of vitamin D status to regulate Na-SO4 cotransport appears to be a direct effect, and is not mediated by the effects of vitamin D on plasma calcium or parathyroid hormone levels. Because sulfate is required for synthesis of essential matrix components, abnormal sulfate metabolism in vitamin D-deficient animals may contribute to producing some of the abnormalities observed in rickets and osteomalacia.
为探究维生素D状态调节硫酸盐稳态的可能性，我们对维生素D缺乏（D-D-）大鼠以及通过补充维生素D或钙/乳糖而血钙正常的D-D-大鼠，评估了血浆硫酸盐水平、肾脏硫酸盐排泄以及肾脏钠-硫酸盐共转运蛋白的表达。D-D-大鼠的血浆硫酸盐水平显著低于对照动物（分别为0.93±0.01和1.15±0.05 mM，P<0.05），与对照大鼠相比，D-D-大鼠的肾脏硫酸盐排泄分数约高两倍。在D-D-大鼠中还观察到，肾皮质刷状缘膜钠-硫酸盐共转运活性降低，同时肾脏钠-硫酸盐共转运蛋白和mRNA含量也平行下降（分别比对照值降低78±3%和73±3%）。补充维生素D后，血浆硫酸盐、硫酸盐排泄分数以及肾脏钠-硫酸盐共转运mRNA和蛋白均恢复正常。相比之下，尽管喂食补充乳糖和钙饮食的维生素D缺乏大鼠血钙正常，且甲状旁腺激素、25(OH)-维生素D和1,25(OH)2-维生素D水平显著低于补充维生素D的组，但这些大鼠的肾脏硫酸盐排泄以及肾脏钠-硫酸盐共转运活性、蛋白丰度和mRNA仍降低。这些结果表明，维生素D调节肾脏钠-硫酸盐共转运和硫酸盐稳态。维生素D状态调节钠-硫酸盐共转运的能力似乎是一种直接作用，并非由维生素D对血钙或甲状旁腺激素水平的影响介导。由于合成必需基质成分需要硫酸盐，维生素D缺乏动物中异常的硫酸盐代谢可能导致佝偻病和骨软化症中观察到的一些异常情况。
