Induction of the vitamin D 24-hydroxylase (CYP24) by 1,25-dihydroxyvitamin D3 is regulated by parathyroid hormone in UMR106 osteoblastic cells

被引:53
作者
Armbrecht, HJ
Hodam, TL
Boltz, MA
Partridge, NC
Brown, AJ
Kumar, VB
机构
[1] St Louis VA Med Ctr, Ctr Geriatr Res Educ & Clin, St Louis, MO 63125 USA
[2] St Louis Univ, Hlth Sci Ctr, Div Geriatr Med, St Louis, MO 63103 USA
[3] St Louis Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, St Louis, MO 63103 USA
[4] St Louis Univ, Hlth Sci Ctr, Dept Pharmacol & Physiol Sci, St Louis, MO 63103 USA
[5] Washington Univ, Sch Med, Div Renal, St Louis, MO 63110 USA
关键词
D O I
10.1210/en.139.8.3375
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The expression of the vitamin D 24-hydroxylase is highly regulated in target tissues for 1,25-dihydroxyvitamin D-3 (1, 25(OH)(2)D), where it may modulate the action of 1,25(OH)(2)D. In UMR106 osteoblastic cells, 1,25(OH)(2)D and PTH synergistically induce 24-hydroxylase expression. The purpose of these studies was to characterize the interaction between 1,25(OH)(2)D and PTH with regard to the messenger RNA (mRNA) levels of the cytochrome P450 component of the 24-hydroxylase (CYP24). PTH alone had no effect on CYP24 mRNA levels, and 1,25(OH)(2)D alone produced only a modest increase. However, 1,25(OH)(2)D and PTH together synergistically increased CYP24 mRNA levels 3-fold compared with 1,25(OH)(2)D alone. PTH also increased the sensitivity of UMR cells to 1,25(OH)(2)D from 10(-8) to 10(-10) M. PTH worked through the cAMP signaling pathway as evidenced by the lack of effect of PTH (3-34) and by the full activity of 8-bromo-cAMP. PTH in the presence of 1,25(OH)(2)D increased CYP24 gene transcription as shown by nuclear run-on studies and by activation of a CYP24 promoter-reporter construct after transfection. PTH also increased vitamin D receptor number in UMR cells, but this occurred at times later than the increase in transcription. These studies demonstrate that PTH in the presence of 1,25(OH)(2)D works through the cAMP-dependent signaling pathway to increase transcription of the CYP24 gene, to increase CYP24 protein levels, and to increase 24-hydroxylase activity.
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页码:3375 / 3381
页数:7
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