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-d ihydroxyvitamin D-3 under conditions of calcium supplementation and ca lcium restriction. Vitamin D-deficient, male weanling rats, fed a calc ium-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 t o 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, b oth vitamin D and 1,25-dihydroxyvitamin D-3 increased receptor levels by 130%. After 8 weeks, 1,25-dihydroxyvitamin D-3 had increased the re ceptor level by 260% while vitamin D had no further effect. Thus, diet ary calcium is required for vitamin D to up-regulate the renal vitamin D receptor level. Further, 1,25-dihydroxyvitamin D-3 itself appears t o have a marked ability to increase vitamin D receptor levels. These r esults suggest a complex mechanism of homologous regulation of the vit amin D receptor in the kidney.