Comparison of the relative effects of 1,24-dihydroxyvitamin D(2) [1, 24-(OH)(2)D(2)], 1,24-dihydroxyvitamin D(3) [1,24-(OH)(2)D(3)], and 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] on selected vitamin D-regulated events in the rat

Biochem Pharmacol. 2000 Sep 1;60(5):701-8. doi: 10.1016/s0006-2952(00)00378-6.


The present experiments were conducted to compare the relative hypercalciuric and hypercalcemic activities of 1,24-dihydroxyvitamin D(2) [1,24-(OH)(2)D(2)], 1,24-dihydroxyvitamin D(3) [1, 24-(OH)(2)D(3)], and 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] in 7-week-old rats. The rats were dosed orally with each sterol for 7 days at a rate of 1 ng/g body weight/day. We also monitored the effect of the three compounds on the induction of mRNA for CaATPase and for 25-hydroxyvitamin D-24-hydroxylase in the kidney and intestine, on plasma vitamin D metabolite levels, and on the capacity to evoke modification in the vitamin D receptor/retinoic acid X receptor (VDR/RXR) heterodimer conformation. Plasma calcium was elevated in the rats treated with 1,24-(OH)(2)D(3) and 1, 25-(OH)(2)D(3), but not in the 1,24-(OH)(2)D(2)-dosed rats. Urinary calcium was elevated significantly (relative to controls) in all groups. The order of hypercalciuric activity was 1,25-(OH)(2)D(3) >/= 1,24-(OH)(2)D(3) >/= 1,24-(OH)(2)D(2) > control. Duodenal plasma membrane calcium ATPase (PMCA) mRNA was elevated to a similar extent in all groups relative to controls. Duodenal 24-hydroxylase mRNA was elevated in all groups relative to controls; however, the elevations were significantly higher in the 1,24-(OH)(2)D(3) and 1, 25-(OH)(2)D(3) groups compared with the 1,24-(OH)(2)D(2) group. Kidney 24-hydroxylase also was elevated significantly in the 1, 24-(OH)(2)D(3)- and 1,25-(OH)(2)D(3)-treated rats but not in the 1, 24-(OH)(2)D(2)-treated rats. Recombinant human vitamin D receptor (hVDR) extracts were incubated with saturating concentrations of 1, 24-(OH)(2)D(2), 1,24-(OH)(2)D(3), and 1,25-(OH)(2)D(3) and subsequently analyzed by electrophoretic mobility shift assay (EMSA). Overall binding was comparable for all metabolites; however, the 1, 24-(OH)(2)D(2) complex exhibited distinctly altered mobility relative to 1,24-(OH)(2)D(3) and 1,25-(OH)(2)D(3), suggestive of an effect on hVDR/hRXR conformation. These data suggest that 1, 24-(OH)(2)D(2) is not as potent as either of the vitamin D(3) sterols at affecting hypercalcemia or hypercalciuria in young growing rats; however, 1,24-(OH)(2)D(2) can evoke other biological responses similar to the vitamin D(3) sterols. These different responses may be related to the alterations in conformation state of the hVDR/hRXR heterodimer.

Publication types

  • Comparative Study

MeSH terms

  • Analysis of Variance
  • Animals
  • Binding, Competitive
  • Calcitriol / adverse effects
  • Calcitriol / pharmacology*
  • Calcium / blood*
  • Dihydroxycholecalciferols / adverse effects
  • Dihydroxycholecalciferols / pharmacology*
  • Ergocalciferols / adverse effects
  • Ergocalciferols / pharmacology*
  • Hypercalcemia / blood
  • Hypercalcemia / chemically induced
  • Male
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Calcitriol / drug effects
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism*
  • Vitamin D / analogs & derivatives
  • Vitamin D / metabolism
  • Vitamin D / pharmacology*


  • Dihydroxycholecalciferols
  • Ergocalciferols
  • RNA, Messenger
  • Receptors, Calcitriol
  • 1,24-dihydroxyvitamin D2
  • Vitamin D
  • 1 alpha,24-dihydroxyvitamin D3
  • Calcitriol
  • Calcium