Dysregulation of vitamin D metabolism in the brain and myocardium of rats following prolonged exposure to dexamethasone
Dysregulation of vitamin D metabolism in the brain and myocardium of rats following prolonged exposure to dexamethasone
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DOI：
10.1007/s00213-014-3440-6
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发表时间：
2014-09-01
影响因子：
3.4
通讯作者：
Zhang, Li-Hong
中科院分区：
文献类型：
--
作者：
Jiang, Pei;Xue, Ying;Zhang, Li-Hong
慢性压力或皮质醇增多症可能会增加抑郁症、心脏疾病和骨质疏松症的风险，这些疾病也与维生素D（VD）缺乏有关。糖皮质激素受体（GR）和维生素D受体（VDR）分布广泛，影响人体生理的许多方面。两种激素之间的相互作用是普遍的，但糖皮质激素对循环VD和局部VD代谢的影响仍然是模糊的，为了填补这一关键空白，我们评估了两种不同剂量的糖皮质激素治疗大鼠的循环VD和脑和心肌VD内分泌系统的变化（0.2和2 mg/kg/天，每天用2 mg/kg的地塞米松（Dex）治疗10天，诱导大鼠抑郁，并降低前额叶皮层和海马中VDR和参与VD激活（CYP 27 B1）和catalysis（CYP 24 A1）的细胞色素P450酶的表达。Dex 0.2mg/kg可增加前额叶VDR的表达，抑制海马CYP 27 B1/CYP 24 A1/VDR的表达。同样，在心肌中，Dex处理的大鼠显示出显著较低的CYP 27 B1/CYP 24 A1/VDR表达。在0.2 mg/kg Dex给药大鼠中，肾脏VD代谢和血清VD状态未发生变化。然而，较高剂量的糖皮质激素抑制了参与VD代谢的三个关键参与者，但没有改变血清VD水平。这些数据提供了新的证据，表明糖皮质激素可以影响VD在脑和心肌中的内分泌作用，这表明VD可能参与糖皮质激素过量引起的神经和心脏功能障碍。
Chronic stress or hypercortisolism may increase the risks of depression, cardiac disorders, and osteoporosis, which are also associated with vitamin D (VD) deficiency. Both glucocorticoid receptor (GR) and vitamin D receptor (VDR) are widely distributed and affect many aspects of human physiology. The cross talk between the two steroids is pervasive, but the effect of glucocorticoids on circulating VD and local VD metabolism remains elusive.To fill this critical gap, we assessed the alterations of circulating VD and VD intracrine system in the brain and myocardium of rats treated with two different doses (0.2 and 2 mg/kg/day, respectively) of dexamethasone (Dex).Daily treatment with 2 mg/kg of Dex for 10 days induced the rats to a depressive-like state and decreased the expression of both VDR and the cytochromes P450 enzymes involved in VD activation (CYP27B1) and catabolism (CYP24A1) in the prefrontal cortex and hippocampus. Meanwhile, the dose of 0.2 mg/kg Dex increased the expression of VDR in the prefrontal cortex but inhibited CYP27B1/CYP24A1/VDR expression in the hippocampus. Similarly, in the myocardium, the rats treated with Dex showed significantly lower expression of CYP27B1/CYP24A1/VDR. Renal VD metabolism and serum VD status were unchanged in 0.2 mg/kg Dex-treated rats. However, the higher dose suppressed the three key players involved in VD metabolism but did not alter serum VD levels.These data provide new evidence that glucocorticoids could affect intracrine actions of VD in the brain and myocardium, which suggests the potential involvement of VD in the neural and cardiac dysfunctions induced by glucocorticoid excess.