The vitamin D receptor in the proximal renal tubule is a key regulator of serum 1α,25-dihydroxyvitamin D3

It is well established that the mitochondria of proximal convoluted tubule cells of the kidney are the site of production of circulating 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3]. The production of 1,25(OH)(2)D-3 at this site is tightly regulated. Parathyroid hormone markedly stimulates 1,25(OH)(2)D-3 production, whereas 1,25(OH)(2)D-3 itself suppresses production. The mechanism of suppression by 1,25(OH)(2)D-3 has not yet been elucidated. We have now found that in the absence of vitamin D (vitamin D deficiency), the vitamin D receptor (VDR) is found in the interior of the apical brush border of the proximal tubule cells. This is unique for the proximal tubule cells, since this has not been observed in the distal tubule cells or in other epithelial cells, such as intestinal mucosa. Administration of 1,25(OH)(2)D-3 to vitamin D-deficient rats results in the movement of VDR from the brush border to the cytoplasm and nucleus presumably bound to reabsorbed 1,25(OH)(2)D-3. The VDR bound to 1,25(OH)(2)D-3 suppresses expression of 25-hydroxyvitamin D-3 1 alpha-hydroxylase and stimulates the 25-hydroxyvitamin D-3 24-hydroxylase. Thus, VDR in the apical brush border of the proximal convoluted tubule cells serves to sense the level of circulating 1,25(OH)(2)D-3 and modulates the activity of the 1 alpha-hydroxylase and the 24-hydroxylase accordingly.