title: The vitamin D receptor in the proximal renal tubule is a key regulator of serum 1α,25-dihydroxyvitamin D₃.
abstract: It is well established that the mitochondria of proximal convoluted tubule cells of the kidney are the site of production of circulating 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The production of 1,25(OH)2D3 at this site is tightly regulated. Parathyroid hormone markedly stimulates 1,25(OH)2D3 production, whereas 1,25(OH)2D3 itself suppresses production. The mechanism of suppression by 1,25(OH)2D3 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)2D3 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)2D3. The VDR bound to 1,25(OH)2D3 suppresses expression of 25-hydroxyvitamin D3 1α-hydroxylase and stimulates the 25-hydroxyvitamin D3 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)2D3 and modulates the activity of the 1α-hydroxylase and the 24-hydroxylase accordingly.
authors.affiliation: Department of Biochemistry, University of Wisconsin, Madison, Wisconsin; and Vitamin D Research Institute, Shaanxi University of Technology, Shaanxi Province, China.
authors.forename: Yongji
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, University of Wisconsin, Madison, Wisconsin; and.
authors.forename: Jinge
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry, University of Wisconsin, Madison, Wisconsin; and deluca@biochem.wisc.edu.
authors.forename: Hector F
authors.initials: HF
authors.lastname: DeLuca
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000097:blood; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000378:metabolism / Q000502:physiology*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D018167:Receptors, Calcitriol; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002118:Calcium
keywords: 1,25-dihydroxyvitamin D; 1α-hydroxylase; 24-hydroxylase; calcium; proximal renal tubule; vitamin D receptor