A possible role of vitamin D receptors in regulating vitamin D activation in the kidney.
The vitamin D endocrine system is regulated reciprocally by renal 25-hydroxyvitamin D3 1 alpha- and 24-hydroxylases. Previously, we reported that renal proximal convoluted tubules, the major site of 1 alpha, 25-dihydroxyvitamin D3 production, have vitamin D receptors. In the presence of vitamin D receptors, renal proximal convoluted tubules cannot maintain the state of enhanced production of 1 alpha, 25-dihydroxyvitamin D3. To clarify this discrepancy, we proposed a working hypothesis for the reciprocal control of renal 25-hydroxyvitamin D3 1 alpha- and 24-hydroxylase activities. In rat models of enhanced renal production of 1 alpha, 25-dihydroxyvitamin D3, expression of vitamin D receptors and 25-hydroxyvitamin D3 24-hydroxylase mRNAs was strikingly suppressed in renal proximal convoluted tubules but not in the cortical collecting ducts. In vitamin D-deficient rats with up-regulated renal 25-hydroxyvitamin D3 1 alpha-hydroxylase activity, expression of vitamin D receptor mRNA in renal proximal convoluted tubules was also down-regulated, indicating that the down-regulation of vitamin D receptor mRNA is not the result of the enhanced production of 1 alpha, 25-dihydroxyvitamin D3. In Japanese quail models with up-regulated renal 25-hydroxyvitamin D3 1 alpha-hydroxylase activity by sex steroids, expression of vitamin D receptor mRNA was also down-regulated in the kidney but not in the duodenum. These results suggest that the down-regulation of vitamin D receptors plays a critical role in production of 1 alpha, 25-dihydroxyvitamin D3 in renal proximal convoluted tubules.
Iida
K
K
Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
Shinki
T
T
Yamaguchi
A
A
DeLuca
H F
HF
Kurokawa
K
K
Suda
T
T
D000818:Animals; D015139:Blotting, Southern; D002117:Calcitriol / Q000096:biosynthesis; D002118:Calcium / Q000097:blood; D003370:Coturnix; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004386:Duodenum / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D007668:Kidney / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D007672:Kidney Cortex / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008297:Male; D009399:Nephrons / Q000187:drug effects / Q000378:metabolism; D015345:Oligonucleotide Probes; D010281:Parathyroid Hormone / Q000097:blood; D016105:Parathyroidectomy; D010758:Phosphorus / Q000097:blood; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000502:physiology*; D013250:Steroid Hydroxylases / Q000096:biosynthesis*; D013965:Thyroidectomy; D014807:Vitamin D / Q000378:metabolism* / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000503:physiopathology*; D065668:Vitamin D3 24-Hydroxylase
D015345:Oligonucleotide Probes; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D014807:Vitamin D; D010758:Phosphorus; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol; D002118:Calcium