25-Hydroxyvitamin D3 is an agonistic vitamin D receptor ligand

Yan Ru Lou*, Ferdinand Molnár, Mikael Peräkylä, Shengjun Qiao, Allan V. Kalueff, René St-Arnaud, Carsten Carlberg, Pentti Tuohimaa

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

135 Citations (Scopus)


25-Hydroxyvitamin D3 1α-hydroxylase encoded by CYP27B1 converts 25-hydroxyvitamin D3 into 1α,25-dihydroxyvitamin D3, a vitamin D receptor ligand. 25-Hydroxyvitamin D3 has been regarded as a prohormone. Using Cyp27b1 knockout cells and a 1α-hydroxylase-specific inhibitor we provide in four cellular systems, primary mouse kidney, skin, prostate cells and human MCF-7 breast cancer cells, evidence that 25-hydroxyvitamin D3 has direct gene regulatory properties. The high expression of megalin, involved in 25-hydroxyvitamin D3 internalisation, in Cyp27b1-/- cells explains their higher sensitivity to 25-hydroxyvitamin D3. 25-Hydroxyvitamin D3 action depends on the vitamin D receptor signalling supported by the unresponsiveness of the vitamin D receptor knockout cells. Molecular dynamics simulations show the identical binding mode for both 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 with the larger volume of the ligand-binding pocket for 25-hydroxyvitamin D3. Furthermore, we demonstrate direct anti-proliferative effects of 25-hydroxyvitamin D3 in human LNCaP prostate cancer cells. The synergistic effect of 25-hydroxyvitamin D3 with 1α,25-dihydroxyvitamin D3 in Cyp27b1-/- cells further demonstrates the agonistic action of 25-hydroxyvitamin D3 and suggests that a synergism between 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 might be physiologically important. In conclusion, 25-hydroxyvitamin D3 is an agonistic vitamin D receptor ligand with gene regulatory and anti-proliferative properties.

Original languageEnglish
Pages (from-to)162-170
Number of pages9
JournalJournal of Steroid Biochemistry and Molecular Biology
Issue number3
Publication statusPublished - 15 Feb 2010
Externally publishedYes


  • Calcidiol
  • Cellular growth
  • CYP27B1
  • Gene regulation
  • Molecular dynamics simulation


Dive into the research topics of '25-Hydroxyvitamin D3 is an agonistic vitamin D receptor ligand'. Together they form a unique fingerprint.

Cite this