Genomic actions of 1,25-dihydroxyvitamin D3

G. K. Whitfield, J. C. Hsieh, P. W. Jurutka, S. H. Selznick, C. A. Haussler, P. N. MacDonald, M. R. Haussler

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Abstract

Recent studies have identified a heterodimer of the vitamin D receptor (VDR) and the retinoid X receptor (RXR) as the active complex for mediating positive transcriptional effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active hormonal form of vitamin D. The VDR-RXR heterodimer has been shown to bind to direct repeat vitamin D-responsive elements (VDREs) upstream of positively controlled genes in the target tissues for vitamin D, including bone (osteocalcin, osteopontin, and β3 integrin), kidney (24-hydroxylase) and intestine (calbindin). Residues that participate in heterodimer formation have been identified in the C-terminal hormone-binding domain by analysis of VDR mutants. The role of the 1,25(OH)2D3 ligand in transcriptional activation by the VDR-RXR heterodimer is not entirely clear, but studies of two natural VDR mutants suggest that the binding of both hormone and RXR are required to induce a receptor conformation that is competent to activate transcription. A final level of complexity is added by recent observations that VDR is modified by phosphorylation. Thus, the VDR-mediated action of 1,25(OH)2D3 is now known to involve multiple factors that may provide a conceptual basis for future understanding of the tissue-specific genomic effects of 1,25(OH)2D3.

Original languageEnglish (US)
Pages (from-to)1690S-1694S
JournalJournal of Nutrition
Volume125
Issue number6 SUPPL.
StatePublished - Jan 1 1995

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Keywords

  • heterodimers
  • steroid hormone receptors
  • transcriptional regulation
  • vitamin D

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Whitfield, G. K., Hsieh, J. C., Jurutka, P. W., Selznick, S. H., Haussler, C. A., MacDonald, P. N., & Haussler, M. R. (1995). Genomic actions of 1,25-dihydroxyvitamin D3. Journal of Nutrition, 125(6 SUPPL.), 1690S-1694S.