25-hydroxyvitamin D(3)-1alpha-hydroxylase expression in normal and pathological parathyroid glands.
25-hydroxyvitamin D(3)-1alpha-hydroxylase expression in normal and pathological parathyroid glands.
复制标题
正常和病理性甲状旁腺中 25-羟基维生素 D(3)-1α-羟化酶的表达。
DOI：
--
复制
发表时间：
2002
影响因子：
5.8
通讯作者：
G. Westin
中科院分区：
文献类型：
--
作者：
U. Segersten;P. Correa;M. Hewison;P. Hellman;H. Dralle;T. Carling;G. Åkerström;G. Westin
活性维生素D， 1,25-二羟基维生素D(3) [1,25(OH)(2)D(3)]，在钙稳态和骨代谢中起关键作用。1,25(OH)(2)D(3)的循环水平被认为主要依赖于肾细胞色素P450酶25-羟基维生素D(3)-1 α -羟化酶（1 α -羟化酶）的活性，这是由甲状旁腺激素强烈诱导的。然而，在几个肾外部位也报道了1 α -羟化酶的活性或表达，在这些部位，局部合成的1,25(OH)(2)D(3)似乎完成了自分泌或旁分泌的功能。这包括胎盘和大脑等组织，它们也表达LRP-2/ meggalin，这是一种多种配体的内吞受体，参与肾脏对1 α -羟化酶25-羟基维生素D底物的摄取(3)。我们之前已经在甲状旁腺细胞中证实了LRP-2/ meggalin，在这里我们展示了RT-PCR和免疫组织化学分析的结果，显示正常和病理甲状旁腺组织中1 α -羟化酶的一致表达。实时定量RT-PCR分析显示，与正常甲状旁腺组织相比，1 α -羟化酶mRNA在大多数甲状旁腺腺瘤和继发性增生性腺体中表达较高，而在甲状旁腺癌中表达较低。研究结果表明，除了循环1,25(OH)(2)D(3)水平的反馈控制外，甲状旁腺细胞还可能受到局部1 α -羟化酶活性的影响，可能具有生长调节和分化作用。
Active vitamin D, 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], plays a pivotal role in calcium homeostasis and bone metabolism. Circulating levels of 1,25(OH)(2)D(3) are thought to be dependent mainly on the activity of the renal cytochrome P450 enzyme 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-hydroxylase), which is potently induced by PTH. However, 1alpha-hydroxylase activity or expression has also been reported at several extrarenal sites, at which local synthesis of 1,25(OH)(2)D(3) appears to fulfill autocrine or paracrine functions. This includes tissues such as placenta and brain that also express LRP-2/megalin, an endocytic receptor for multiple ligands, which is involved in the renal uptake of the substrate for 1alpha -hydroxylase, 25-hydroxyvitamin D(3). We have previously demonstrated LRP-2/megalin in parathyroid cells, and here we present results from RT-PCR and immunohistochemical analyses showing coincident expression of 1alpha-hydroxylase in normal and pathological parathyroid tissue. With real-time quantitative RT-PCR analysis, the expression of 1alpha-hydroxylase mRNA was higher in the majority of parathyroid adenomas and secondary hyperplastic glands but lower in parathyroid carcinomas, compared with normal parathyroid tissue. The findings imply that in addition to feedback control by circulating 1,25(OH)(2)D(3) levels, parathyroid cells may also be influenced by local 1alpha -hydroxylase activity with possible growth regulatory and differentiating effects.