Possible involvement of pregnane X receptor–enhanced CYP24 expression in drug-induced osteomalacia
J. Clin. Invest. Jean Marc Pascussi, et al. 115:177 doi:10.1172/JCI21867 [Go to this article.]

Figure 3
In vivo modulation of CYP24 by PXR agonists. (A and B) Effect of pregnenolone 16α-carbonitrile and dexamethasone on cyp24 mRNA abundance. Mice (n = 5) were injected i.p. for 6 consecutive days with dexamethasone (DEX; 10 mg/kg/d), pregnenolone 16α-carbonitrile (PCN; 100 mg/kg), or corn oil (UT). Total RNA from liver or kidney was prepared, and 1 μg was reverse-transcribed. The relative levels of cyp3a11 and cyp24 mRNAs were determined in duplicate for each mouse by real-time PCR using cyp3a11-specific (A) and cyp24-specific (B) primers. Cyclophilin mRNA levels were used as a reference standard. Data are means ± SE of the ratio of mRNA levels in treated mice to corresponding levels in untreated mice, normalized with respect to cyclophilin mRNA levels. (C and D) Effect of pregnenolone 16α-carbonitrile on vitamin D₃ metabolites in mouse plasma. Mice (n = 5) were injected i.p. for 6 consecutive days with pregnenolone 16α-carbonitrile (100 mg/kg) or corn oil and plasma samples. Pooled mouse plasma (1–2 mice, 300 μl, n = 3) or 50-μl plasma samples (n = 5) were analyzed for 24,25(OH)₂D₃ (C) or 25(OH)D₃ metabolites (D), respectively, as described in Methods. Statistically significant expressions compared with untreated mice are marked with asterisks: *P < 0.05, **P < 0.01, and ***P < 0.005. Fold change relative to control mice is indicated.