Hostname: page-component-8448b6f56d-wq2xx Total loading time: 0 Render date: 2024-04-19T22:14:50.670Z Has data issue: false hasContentIssue false
  • English
  • Français

Age-related alteration of vitamin D metabolism in response to low-phosphate diet in rats

Published online by Cambridge University Press:  08 March 2007

Tsui-Shan Chau ,
Wan-Ping Lai ,
Pik-Yuen Cheung ,
Murray J. Favus  and
Man-Sau Wong
Tsui-Shan Chau
Affiliation:
Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PRC
Wan-Ping Lai
Affiliation:
Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PRC
Pik-Yuen Cheung
Affiliation:
Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PRC
Murray J. Favus
Affiliation:
Section of Endocrinology, Department of Medicine, The University of Chicago, Chicago, IL 60 637, USA
Man-Sau Wong*
Affiliation:
Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PRC
*
*Corresponding author: Dr Man-Sau Wong, fax +852 23649932, email bcmswong@polyu.edu.hk
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The responses of renal vitamin D metabolism to its major stimuli alter with age. Previous studies showed that the increase in circulating 1,25-dihydroxyvitamin D (1,25(OH)2D3) as well as renal 25-hydroxyvitamin D3 1-α hydroxylase (1-OHase) activity in response to dietary Ca or P restriction reduced with age in rats. We hypothesized that the mechanism involved in increasing circulating 1,25(OH)2D3 in response to mineral deficiency alters with age. In the present study, we tested the hypothesis by studying the expression of genes involved in renal vitamin D metabolism (renal 1-OHase, 25-hydroxyvitamin D 24-hydroxylase (24-OHase) and vitamin D receptor (VDR)) in young (1-month-old) and adult (6-month-old) rats in response to low-phosphate diet (LPD). As expected, serum 1,25(OH)2D3 increased in both young and adult rats upon LPD treatment and the increase was much higher in younger rats. In young rats, LPD treatment decreased renal 24-OHase (days 1–7, P<0·01) and increased renal 1-OHase mRNA expression (days 1–5, P<0·01). LPD treatment failed to increase renal 1-OHase but did suppress 24-OHase mRNA expression (P<0·01) within 7 d of LPD treatment in adult rats. Renal expression of VDR mRNA decreased with age (P<0·001) and was suppressed by LPD treatment in both age groups (P<0·05) Feeding of adult rats with 10 d of LPD increased 1-OHase (P<0·05) and suppressed 24-OHase (P<0·001) as well as VDR (P<0·05) mRNA expression. These results indicate that the increase in serum 1,25(OH)2D3 level in adult rats during short-term LPD treatment is likely to be mediated by a decrease in metabolic clearance via the down-regulation of both renal 24-OHase and VDR expression. The induction of renal 1-OHase mRNA expression in adult rats requires longer duration of LPD treatment than in younger rats.

Keywords

25-Hydroxyvitamin D3 1-α hydroxylase25-Hydroxyvitamin D3 24 hydroxylaseVitamin D receptorLow-phosphate dietAdult rats
Type
Research Article
Information
British Journal of Nutrition , Volume 93 , Issue 3 , March 2005 , pp. 299 - 307
Copyright
Copyright © The Nutrition Society 2005

References

Akiyoshi-Shibata, M, Sakaki, T, Ohyama, Y, Noshiro, M, Okuda, K & Yabusaki, Y (1994) Further oxidation of hydroxycalcidiol by calcidiol 24-hydroxylase. Eur J Biochem 224, 335–343.CrossRefGoogle ScholarPubMed
Armbrecht, HJ, Forte, LR & Halloran, BP (1984) Effect of age and dietary calcium on renal 25(OH)D metabolism, serum 1,25(OH)2D, and PTH. Am J Physiol 246, E266–E270.Google Scholar
Armbrecht, HJ, Boltz, MA & Hodam, TL (2003) PTH increases renal 25(OH)D3 -1α-hydroxylase (CYP1α) mRNA but not renal 1,25(OH)2D3 production in adult rats. Am J Physiol Renal Physiol 284, F1032–F1036.CrossRefGoogle Scholar
Armbrecht, HJ, Hodam, TL, Boltz, MA & Kumar, VB (1999) Capacity of a low calcium diet to induce the renal vitamin D 1α-hydroxylase is decreased in adult rats. Biochem Biophys Res Commun 255, 731–734.CrossRefGoogle Scholar
Armbrecht, HJ, Wongsurawat, N, Zenser, TV & Davis, BB (1982) Differential effects of parathyroid hormone on the renal 1,25-dihydroxyvitamin D 3 and 24,25-dihydroxyvitamin D 3 production of young and adult rats. Endocrinology 111, 1339–1344.CrossRefGoogle Scholar
Armbrecht, HJ, Zenser, TV & Davis, BB (1980) Effect of age on the conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 by kidney of rat. J Clin Invest 66, 1118–1123.CrossRefGoogle ScholarPubMed
Avioli, LV, McDonald, JE & Lee, SW (1965) The influence of age on the intestinal absorption of 47Ca in women and its relation to 47Ca absorption in postmenopausal women. J Clin Invest 44, 1960–1967.CrossRefGoogle Scholar
Beckman, MJ & DeLuca, HK (2002) Regulation of renal vitamin D receptor is an important determinant of 1alpha,25-dihydroxyvitamin D(3) levels in vivo. Arch Biochem Biophys 401, 44–52.CrossRefGoogle Scholar
Clemens, TL, Zhou, XY, Myles, M, Endres, D & Lindsay, R (1986) Serum vitamin D2 and vitamin D3 metabolite concentrations and absorption of vitamin D2 in elderly subjects. J Clin Endocrinol Metab 63, 656–660.CrossRefGoogle ScholarPubMed
Condamine, L, Vrtovsnik, F, Friedlander, G & Garabedian, M (1994) Local action of phosphate depletion and insulin-like growth factor 1 on in vitro production of 1,25-dihydroxyvitamin D by cultured mammalian kidney cells. J Clin Invest 94, 1673–1679.CrossRefGoogle Scholar
Dick, IM, Retallack, R & Prince, RL (1990) Rapid nongenomic inhibition of renal 25-hydroxyvitamin D3 1-hydroxylase by 1,25-dihydroxyvitamin D3. Am J Physiol 259, E272–E277.Google Scholar
Favus, MJ & Tembe, V (1992) The use of pharmacologic agents to study mechanisms of intestinal calcium transport. J Nutr 122, Suppl., 683–686.CrossRefGoogle ScholarPubMed
Friedlander, J, Janulis, M, Tembe, V, Ro, HK, Wong, MS & Favus, MJ (1994) Loss of parathyroid hormone stimulated 1,25(OH)2D3 production in aging does not involve protein kinase A or protein kinase C pathways. J Bone Miner Res 9, 339–345.CrossRefGoogle Scholar
Gallagher, JC, Riggs, BL, Eisman, JA, Hamstra, A, Arnaud, SB & Deluca, HF (1979) Intestinal calcium absorption and serum vitamin D metabolites in normal subjects and osteoporotic patients. J Clin Invest 64, 729–736.CrossRefGoogle ScholarPubMed
Garabedian, M, Holick, MF, DeLuca, HF & Boyle, BL (1972) Control of 25-hydroxycholecalciferol metabolism by parathyroid glands. Proc Natl Acad Sci USA 69, 1673–1676.CrossRefGoogle ScholarPubMed
Gray, RW (1987) Evidence that somatomedins mediate the effect of hypophosphatemia to increase serum 1,25-dihydroxyvitamin D 3 level in rats. Endocrinology 121, 504–512.CrossRefGoogle Scholar
Gray, RW & Gambert, SR (1982) Effect of age on plasma 1,25(OH)2 vitamin D in the rat. Age 5, 54–56.CrossRefGoogle Scholar
Gray, RW & Garthwaite, TL (1985) Activation of renal 1,25-dihydroxyvitamin D3 synthesis by phosphate deprivation: evidence for a role for growth hormone. Endocrinology 116, 189–193.CrossRefGoogle ScholarPubMed
Healy, KD, Zella, JB, Prahl, JM & DeLuca, HF (2003) Regulation of the murine renal vitamin D receptor by 1,25-dihydroxyvitamin D3 and calcium. Proc Natl Acad Sci USA 100, 9733–9737.CrossRefGoogle ScholarPubMed
Halloran, BP & Spencer, EM (1988) Dietary phosphorus and 1,25-dihydroxyvitamin D metabolism: influence of insulin-like growth factor I. Endocrinology 123, 1225–1229.CrossRefGoogle Scholar
Henry, HL & Norman, AW (1974) Studies on calciferol metabolism. IX. Renal 25-hydroxy-vitamin D3-1 hydroxylase. Involvement of cytochrome P-450 and other properties. J Biol Chem 249, 7529–7535.CrossRefGoogle ScholarPubMed
Hughes, MR, Brumbaugh, PF, Haussler, MR, Wergedal, JE & Baylink, DJ (1975) Regulation of serum 1,25-dihydroxyvitamin D3 by calcium and phosphate in the rat. Science 190, 578–579.CrossRefGoogle Scholar
Jones, G, Strugnell, SA & DeLuca, HF (1998) Current understanding of the molecular actions of vitamin D. Physiol Rev 78, 1193–1231.CrossRefGoogle ScholarPubMed
Lai, WP, Chau, TS, Cheung, PY, Chen, WF, Lo, SCL, Favus, MJ & Wong, MS (2003) Adaptive responses of 25-hydroxyvitamin D3 1-alpha hydroxylase expression to dietary phosphate restriction in young and adult rats. Biochim Biophys Acta 1639, 34–42.CrossRefGoogle ScholarPubMed
Lee, DBN, Brautbar, N, Walling, MW, Silis, V, Oburn, CJW & Kleeman, CR (1979) Effect of phosphorus depletion on intestinal calcium and phosphorus absorption. Am J Physiol 236, E451–E457.Google ScholarPubMed
Malm, OJ, Nickolaysen, R & Skjelkvale, L (1955) Calcium metabolism in old age as related to ageing of the skeleton. In Ageing – General Aspects, Ciba Foundation Colloquia on Ageing, pp. 109–125 [Wolstenholme, GEW and Cameron, MR, editors]. Boston Little, Brown.Google Scholar
Murayama, A, Takeyama, K, Kitanaka, S, Kodera, Y, Kawaguchi, Y, Hosoya, T & Kato, S (1999) Positive and negative regulation of the renal 25-hydroxyvitamin D3 1α-hydroxylase gene by parathyroid hormone, calcitonin, and 1,25(OH)2D3 in intact animals. Endocrinology 140, 2224–2231.CrossRefGoogle ScholarPubMed
National Research Council (1996) Guide for the care and use of laboratory animals. National Academy Press, Washington D.C.Google Scholar
Nesbitt, T & Drezner, MK (1993) Insulin-like growth factor-I regulation of renal 25-hydroxyvitamin D-1-hydroxylase activity. Endocrinology 132, 133–138.CrossRefGoogle ScholarPubMed
Pike, JW, Spanos, E, Colston, KW, Macintyre, I & Haussler, MR (1978) Influence of estrogen on renal vitamin D hydroxylases and serum 1alpha,25-(OH)2D3 in chicks. Am J Physiol 235, E338–E343.Google Scholar
Roy, S & Tenenhouse, HS (1996) Transcriptional regulation and renal localization of 1,25-dihydroxyvitamin D3 -24-hydroxylase gene expression: effects of the Hyp mutation and 1,25-dihydroxyvitamin D 3. Endocrinology 137, 2938–2946.CrossRefGoogle Scholar
Shimada, T, Hasegawa, H, Yamazaki, Y, Muto, T, Hino, R, Takeuchi, Y, Fujita, T, Nakahara, K, Fukumoto, S & Yamashita, T (2004) FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 19, 429–435.CrossRefGoogle ScholarPubMed
Spanos, E, Barrett, D, Maclntyre, I, Pike, JW, Safilian, WF & Haussler, MR (1978) Effect of growth hormone on vitamin D metabolism. Nature 273, 246–247.CrossRefGoogle ScholarPubMed
Tanaka, Y & Deluca, HF (1975) The control of 25-hydroxyvitamin D metabolism by inorganic phosphorus. Arch Biochem Biophys 154, 566–574.CrossRefGoogle Scholar
Takeda, E, Yamamoto, H, Nashiki, K, Sato, T, Arai, H & Taketani, Y (2004) Inorganic phosphate homeostasis and the role of dietary phosphorus. J Cell Mol Med 8, 191–200.CrossRefGoogle ScholarPubMed
Tenenhouse, HS, Martel, J, Gauthier, C, Zhang, MYH & Portale, AA (2001) Renal expression of the sodium/phosphate cotransporter gene, Npt2, is not required for regulation of renal 1a-hydroxylase by phosphate. Endocrinology 142, 1124–1129.CrossRefGoogle ScholarPubMed
Tsai, KS, Heath, HIII, Kumar, R & Riggs, BL (1984) Impaired vitamin D metabolism with aging in women. Possible role in pathogenesis of senile osteoporosis. J Clin Invest 73, 1668–1672.CrossRefGoogle ScholarPubMed
Wilz, DR, Gray, RW, Dominguez, JH & Lemann, J Jr (1979) Plasma 1,25-(OH)2-vitamin D concentrations and net intestinal calcium, phosphate, and magnesium absorption in humans. Am J Clin Nutr 10, 2052–2060.CrossRefGoogle Scholar
Wong, MS, Sriussadaporn, S, Tembe, VA & Favus, MJ (1997) Insulin-like growth factor I increases renal 1,25(OH)2D3 biosynthesis during low-P diet in adult rats. Am J Physiol 272, F698–F703.Google ScholarPubMed
Wong, MS, Tembe, VA & Favus, MJ (2000) Insulin-like growth factor-I stimulates renal 1,25-dihydroxycholecalciferol synthesis in old rats fed a low calcium diet. J Nutr 130, 1147–1152.CrossRefGoogle ScholarPubMed
Wu, S, Finch, J, Zhong, M, Slatopolsky, E, Grieff, M & Brown, AJ (1996) Expression of the renal 25-hydroxyvitamin D-24-hydroxylase gene: regulation by dietary phosphate. Am J Physiol 271, F203–F208.Google ScholarPubMed
Yoshida, T, Toshida, N, Monkawa, T, Hayashi, M & Saruta, T (2001) Dietary phosphorus deprivation induces 25-hydroxyvitamin D3 1α-hydroxylase gene expression. Endocrinology 142, 1720–1726.CrossRefGoogle Scholar
Zhang, MYH, Wang, X, Wang, JT, Compagnone, NA, Mellon, SH, Olson, JL, Tenenhouse, HS, Miller, WL & Portale, AA (2002) Dietary phosphorus transcriptionally regulates 25-hydroxyvitamin D-1α-hydroxylase gene expression in the proximal renal tubule. Endocrinology 143, 587–595.CrossRefGoogle ScholarPubMed