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The present study compared the equimolar efficacies of 1\u03b1\u2010hydroxyvitamin D<jats:sub>3<\/jats:sub> [1\u03b1(OH)D<jats:sub>3<\/jats:sub>] (6\u2009nmol\/kg\u2009i.p. q2d\u2009\u00d7\u20094), a lipophilic precursor with a longer plasma half\u2010life that is converted to 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>, and 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> on vitamin D receptor (VDR) target genes. To clarify whether changes in VDR genes was due to VDR and not secondary, farnesoid X receptor (FXR)\u2010directed effects, namely, lower Cyp7a1 expression in rat liver due to increased bile acid absorption, wildtype [<jats:italic>fxr<\/jats:italic>(+\/+)] and FXR knockout [<jats:italic>fxr<\/jats:italic>(\u2010\/\u2010)] mice were used to distinguish between VDR and FXR effects. With the exception that hepatic Sult2a1 mRNA was increased equally well by 1\u03b1(OH)D<jats:sub>3<\/jats:sub> and 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>, 1\u03b1(OH)D<jats:sub>3<\/jats:sub> treatment led to higher increases in hepatic Cyp7a1, renal Cyp24a1, VDR, Mdr1 and Mrp4, and intestinal Cyp24a1 and Trpv6 mRNA expression in both <jats:italic>fxr<\/jats:italic>(+\/+) and <jats:italic>fxr<\/jats:italic>(\u2010\/\u2010) mice compared to 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> treatment. A similar induction in protein expression and microsomal activity of hepatic Cyp7a1 and renal P\u2010gp and Mrp4 protein expression was noted for both compounds. A higher intestinal induction of Trpv6 was observed, resulting in greater hypercalcemic effect following 1\u03b1(OH)D<jats:sub>3<\/jats:sub> treatment. The higher activity of 1\u03b1(OH)D<jats:sub>3<\/jats:sub> was explained by its rapid conversion to 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> in tissue sites, furnishing higher plasma and tissue 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> levels compared to following 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>\u2010treatment. In conclusion, 1\u03b1(OH)D<jats:sub>3<\/jats:sub> exerts a greater effect on VDR gene induction than equimolar doses of 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> in mice. Copyright \u00a9 2013 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.1856","type":"journal-article","created":{"date-parts":[[2013,7,29]],"date-time":"2013-07-29T13:23:25Z","timestamp":1375104205000},"page":"402-416","source":"Crossref","is-referenced-by-count":10,"title":["Comparative effects of 1\u03b1\u2010hydroxyvitamin D<sub>3<\/sub> and 1,25\u2010dihydroxyvitamin D<sub>3<\/sub> on transporters and enzymes in <i>fxr(+\/+)<\/i> and <i>fxr(\u2010\/\u2010)<\/i> mice"],"prefix":"10.1002","volume":"34","author":[{"given":"Edwin C.Y.","family":"Chow","sequence":"first","affiliation":[{"name":"Leslie Dan Faculty of Pharmacy University of Toronto  Toronto Ontario Canada M5S 3\u2009M2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew R.","family":"Durk","sequence":"additional","affiliation":[{"name":"Leslie Dan Faculty of Pharmacy University of Toronto  Toronto Ontario Canada M5S 3\u2009M2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han\u2010Joo","family":"Maeng","sequence":"additional","affiliation":[{"name":"Leslie Dan Faculty of Pharmacy University of Toronto  Toronto Ontario Canada M5S 3\u2009M2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. 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