Abstract：
:The 25-hydroxyvitamin D(3)-24-hydroxylase mRNA is tightly and reciprocally regulated by 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and parathyroid hormone (PTH). The upregulation of the 24-hydroxylase by 1,25(OH)(2)D(3) is well established and occurs at the transcriptional level through two vitamin D response elements in the promoter of the gene. However, this induction is blocked by the protein synthesis inhibitor cycloheximide (CHX) indicating a protein component in the regulation pathway. CHX treatment reduced total vitamin D receptor (VDR) protein levels in cells, but reintroduction of VDR and/or retinoid X receptor protein into cells by transfection did not reduce the inhibition by CHX. This indicates that production of another transcription factor or mRNA-stabilizing protein synthesized in response to 1,25(OH)(2)D(3) is required for optimal accumulation of 24-hydroxylase mRNA. PTH downregulates the 24-hydroxylase mRNA by affecting its stability. The half-life of 24-hydroxylase mRNA is reduced 4.2-fold in AOK-B50 cells by PTH. Untranslated regions of the 24-hydroxylase mRNA in reporter gene assays did not confer PTH responsiveness. Further analysis of the coding region of the rat 24-hydroxylase may reveal sites of action of PTH.
journal_name
J Cell Biochemjournal_title
Journal of cellular biochemistryauthors
Zierold C,Mings JA,DeLuca HFdoi
10.1002/jcb.10341subject
Has Abstractpub_date
2003-02-01 00:00:00pages
234-7issue
2eissn
0730-2312issn
1097-4644journal_volume
88pub_type
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