PMID- 10927029
OWN - NLM
STAT- MEDLINE
DCOM- 20000828
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 60
IP  - 5
DP  - 2000 Sep 1
TI  - 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.
PG  - 701-8
AB  - 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.
FAU - Horst, R
AU  - Horst R
AD  - USDA-ARS, National Animal Disease Center, Ames, IA 50010, USA. 
      rhorst@nadc.ars.usda.gov
FAU - Prapong, S
AU  - Prapong S
FAU - Reinhardt, T
AU  - Reinhardt T
FAU - Koszewski, N
AU  - Koszewski N
FAU - Knutson, J
AU  - Knutson J
FAU - Bishop, C
AU  - Bishop C
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Dihydroxycholecalciferols)
RN  - 0 (Ergocalciferols)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Calcitriol)
RN  - 124043-51-2 (1,24-dihydroxyvitamin D2)
RN  - 1406-16-2 (Vitamin D)
RN  - 60965-80-2 (1 alpha,24-dihydroxyvitamin D3)
RN  - FXC9231JVH (Calcitriol)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Binding, Competitive
MH  - Calcitriol/adverse effects/*pharmacology
MH  - Calcium/*blood
MH  - Dihydroxycholecalciferols/adverse effects/*pharmacology
MH  - Ergocalciferols/adverse effects/*pharmacology
MH  - Hypercalcemia/blood/chemically induced
MH  - Male
MH  - RNA, Messenger/drug effects/metabolism
MH  - Rats
MH  - Receptors, Calcitriol/drug effects/genetics/*metabolism
MH  - Vitamin D/analogs & derivatives/metabolism/*pharmacology
EDAT- 2000/08/06 11:00
MHDA- 2000/09/02 11:01
CRDT- 2000/08/06 11:00
PHST- 2000/08/06 11:00 [pubmed]
PHST- 2000/09/02 11:01 [medline]
PHST- 2000/08/06 11:00 [entrez]
AID - S0006-2952(00)00378-6 [pii]
AID - 10.1016/s0006-2952(00)00378-6 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2000 Sep 1;60(5):701-8. doi: 10.1016/s0006-2952(00)00378-6.