Regulation of the murine renal vitamin D receptor by 1,25-dihydroxyvitamin D3 and calcium.
Renal vitamin D receptor (VDR) is required for 1,25-dihydroxyvitamin D3-[1,25(OH)2D3]-induced renal reabsorption of calcium and for 1,25(OH)2D3-induced 1,25(OH)2D3 24-hydroxylase. The long-term effect of vitamin D and dietary calcium on the expression of renal VDR was examined in the nonobese diabetic mouse. Vitamin D-deficient and vitamin D-replete mice were maintained on diets containing 0.02%, 0.25%, 0.47%, and 1.20% calcium with or without 50 ng of 1,25(OH)2D3 per day. Vitamin D-replete mice on a 1.20% calcium diet had renal VDR levels of 165 fmol/mg protein. Calcium restriction caused renal VDR levels to decrease to <30 fmol/mg protein in vitamin D-deficient mice and to approximately 80 fmol/mg protein in vitamin D-replete mice. When dietary calcium was present, 50 ng of 1,25(OH)2D3 elevated the VDR levels 2- to 10-fold, depending on vitamin D status and the level of calcium. In the absence of either vitamin D or calcium, the VDR mRNA was expressed at a basal level. 1,25(OH)2D3 supplementation caused relative VDR mRNA to increase 8- to 10-fold in the vitamin D-deficient mouse when dietary calcium was available. This increase was completely absent in the calcium-restricted mice. This in vivo study demonstrates that 1,25(OH)2D3 and calcium are both required for renal VDR mRNA expression above a basal level, furthering our understanding of the complex regulation of renal VDR by 1,25(OH)2D3 and calcium.
Healy
Kevin D
KD
Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
Zella
Julia B
JB
Prahl
Jean M
JM
DeLuca
Hector F
HF
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002136:Calcium, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
D002136:Calcium, Dietary; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol