The necessity for calcium for increased renal vitamin D receptor in response to 1,25-dihydroxyvitamin D

To further investigate the regulation of the vitamin D receptor in the kidney of the rat, we analyzed the response of the receptor to 1,25-dihydroxyvitamin D-3 under conditions of calcium supplementation and calcium restriction. Vitamin D-deficient, male weanling rats, fed a calcium-restricted or calcium-supplemented, vitamin D-deficient diet, were treated for 4 weeks with vitamin D (orally) or 1,25-dihydroxyvitamin D-3 (60 pmol/d by mini-osmotic pump). We also extended the treatment to 8 weeks for one group of animals fed the calcium-supplemented diet. Vitamin D compounds decreased the level of renal receptor in rats fed the low calcium diet. However, in animals given a 1.2% calcium diet, both vitamin D and 1,25-dihydroxyvitamin D-3 increased receptor levels by 130%. After 8 weeks, 1,25-dihydroxyvitamin D-3 had increased the receptor level by 260% while vitamin D had no further effect. Thus, dietary calcium is required for vitamin D to up-regulate the renal vitamin D receptor level. Further, 1,25-dihydroxyvitamin D-3 itself appears to have a marked ability to increase vitamin D receptor levels. These results suggest a complex mechanism of homologous regulation of the vitamin D receptor in the kidney.