Regulation of 25-hydroxyvitamin D3-24-hydroxylase mRNA by 1,25-dihydroxyvitamin D3 and parathyroid hormone.
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.
Zierold
Claudia
C
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 50706-1544, USA.
Mings
Jamie A
JA
DeLuca
Hector F
HF
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006207:Half-Life; D006801:Humans; D010281:Parathyroid Hormone / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D065668:Vitamin D3 24-Hydroxylase
D010281:Parathyroid Hormone; D012333:RNA, Messenger; D014157:Transcription Factors; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase