Regulation of vitamin D-1α-hydroxylase and-24-hydroxylase expression by dexamethasone in mouse kidney
Regulation of vitamin D-1α-hydroxylase and-24-hydroxylase expression by dexamethasone in mouse kidney
复制标题
DOI：
10.1677/joe.0.1640339
复制
发表时间：
2000-03-01
影响因子：
4
通讯作者：
Horiuchi, N
中科院分区：
文献类型：
--
作者：
Akeno, N;Matsunuma, A;Horiuchi, N
我们研究了地塞米松对正常 (NCD) 饮食或缺乏钙和维生素 D (LCD) 饮食的小鼠肾脏中维生素 D-1 α-羟化酶和 -24-羟化酶表达以及维生素 D 受体 (VDR) 含量的影响，为期 2 周。在过去 5 天中，小鼠接受媒介物或地塞米松（皮下注射每天 2 毫克/千克）。在 NCD 和 LCD 组中，地塞米松显着增加血浆钙浓度，而不改变 1,25-二羟基维生素 D-3 (1,25(OH)(2)D-3) 血浆浓度。 NCD 小鼠的 Northern 印迹和酶活性分析显示，地塞米松适度增加肾脏 VDR mRNA 表达，并大大增加 24-羟化酶 mRNA 丰度和酶活性，但不影响 1α-羟化酶 mRNA 丰度和酶活性。在喂食 LCD 饮食的小鼠中，地塞米松使肾脏 VDR mRNA 表达增加 1.5 倍，降低 1α-羟化酶 mRNA 丰度（52%）和活性（34%），并显着增加 α-羟化酶 mRNA 丰度（16 倍）和酶活性（9 倍）。地塞米松治疗不会改变 LCD 小鼠的功能性 VDR 数（B-max 125-141 fmol/mg 蛋白）或配体亲和力（K-d 0.13-0.10 nM）。向NCD小鼠皮下注射1,25(OH)(2)D-3（每天0.24 nmol/kg，持续5天）强烈增加肾脏24-羟化酶mRNA丰度和酶活性，而地塞米松对这些小鼠肾脏24-羟化酶表达没有影响。这可能是由于 1,25(OH)(2)D-3 对 24-羟化酶的强烈诱导。这些发现表明，糖皮质激素诱导的骨质疏松症是由类固醇对骨的直接作用引起的，并且糖皮质激素对肾脏 25-羟基维生素 D-3 代谢的调节作用可能与疾病的发生和进展关系不大。
We investigated the effects of dexamethasone on vitamin D-1 alpha-hydroxylase and -24-hydroxylase expression and on vitamin D receptor (VDR) content in the kidneys of mice fed either a normal (NCD) diet or a calcium- and vitamin D-deficient (LCD) diet for 2 weeks. For the last 5 days mice received either vehicle or dexamethasone (2 mg/kg per day s.c.). Dexamethasone significantly increased plasma calcium concentrations without changing plasma concentrations of 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) in both NCD and LCD groups. Northern blot and enzyme activity analyses in NCD mice revealed that dexamethasone increased renal VDR mRNA expression modestly and greatly increased 24-hydroxylase mRNA abundance and enzyme activity, but did not affect 1 alpha-hydroxylase mRNA abundance and enzyme activity. In mice fed an LCD diet, dexamethasone increased renal VDR mRNA expression 1.5-fold, decreased 1 alpha-hydroxylase mRNA abundance (52%) and activity (34%), and markedly increased -hydroxylase mRNA abundance (16-fold) and enzyme activity (9-fold). Dexamethasone treatment did not alter functional VDR number (B-max 125-141 fmol/mg protein) or ligand affinity (K-d 0.13-0.10 nM) in LCD mice. Subcutaneous injections of 1,25(OH)(2)D-3 (0.24 nmol/kg per day for 5 days) into NCD mice strongly increased renal 24-hydroxylase mRNA abundance and enzyme activity, while there was no effect of dexamethasone on renal 24-hydroxylase expression in these mice. This may be due to overwhelming induction of 24-hydroxylase by 1,25(OH)(2)D-3. These findings suggest that glucocorticoid-induced osteoporosis is caused by direct action of the steroids on bone, and the regulatory effect of glucocorticoids on renal 25-hydroxyvitamin D-3 metabolism may be less implicated in the initiation and progression of the disease.