QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Whitfield, G. K. Articles by Haussler, M. R. Search for Related Content PubMed PubMed Citation Articles by Whitfield, G. K. Articles by Haussler, M. R.

Genomic Actions of 1,25-dihydroxyvitamin D₃^1,2,

Department of Biochemistry, The University of Arizona College of Medicine, Tucson, AZ 85724 ^* Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, St. Louis, MO 63104

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 ß₃ 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.

KEY WORDS: • vitamin D • steroid hormone receptors • transcriptional regulation • heterodimers

¹ Presented as part of the symposium "Pleiotropic Actions of Vitamin D" given at the Experimental Biology '94 meeting, Anaheim, CA, on April 26, 1994. This symposium was sponsored by the American Institute of Nutrition. Guest editor for this symposium was Anthony W. Norman, University of California, Riverside, CA.

² Supported by NIH grants DK-40372 (to G. K. W.) and DK-33351 and AR-15781 (to M. R. H.).

³ To whom correspondence should be addressed: Department of Biochemistry, The University of Arizona College of Medicine, 1501 N. Campbell Avenue, Tucson, AZ 85724.