A possible role of vitamin D receptors in regulating vitamin D activation in the kidney

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 92; no. 13; pp. 6112 - 6116
• Main Authors: Iida, K. (Showa University, Tokyo, Japan.), Shinki, T, Yamaguchi, A, Deluca, H.F, Kurokawa, K, Suda, T
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 20.06.1995; National Acad Sciences; National Academy of Sciences
• Subjects: ACTIVIDAD ENZIMATICA; ACTIVITE ENZYMATIQUE; Animals; ARN MENSAJERO; ARN MESSAGER; Blotting, Southern; CAILLE; Calcitriol - biosynthesis; Calcium; Calcium - blood; Cellular biology; CHIMIORECEPTEUR; CODORNIZ; Coturnix; Cytochrome P-450 Enzyme System - biosynthesis; Diet; Down regulation; Duodenum; Duodenum - metabolism; Endocrine cells; Endocrine system; ESTROGENOS; EXPRESION GENICA; EXPRESSION DES GENES; Gene Expression; Gene Expression Regulation; INTESTIN; INTESTINOS; Kidney - drug effects; Kidney - physiology; Kidney - physiopathology; Kidney Cortex - metabolism; Kidney Tubules, Proximal - metabolism; Kidneys; Male; Messenger RNA; Nephrons - drug effects; Nephrons - metabolism; OESTROGENE; Oligonucleotide Probes; OXIDORREDUCTASAS; OXYDOREDUCTASE; Parathyroid Hormone - blood; Parathyroidectomy; Phosphorus; Phosphorus - blood; Polymerase Chain Reaction; PROTEINAS AGLUTINANTES; PROTEINE DE LIAISON; QUIMIORECEPTORES; RAT; RATA; Rats; Rats, Sprague-Dawley; Receptors; Receptors, Calcitriol - physiology; REIN; Ribonucleic acid; RINONES; RNA; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; Rodents; Steroid Hydroxylases - biosynthesis; Thyroidectomy; Vitamin D; Vitamin D - metabolism; Vitamin D - pharmacology; Vitamin D Deficiency - physiopathology; Vitamin D3 24-Hydroxylase; VITAMINA D; VITAMINE D
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.13.6112

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