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FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis.
J Bone Miner Res. 2004 Mar; 19(3):429-35.JB

Abstract

We analyzed the effects of an FGF-23 injection in vivo. FGF-23 caused a reduction in serum 1,25-dihydroxyvitamin D by altering the expressions of key enzymes for the vitamin D metabolism followed by hypophosphatemia. This study indicates that FGF-23 is a potent regulator of the vitamin D and phosphate metabolism.

INTRODUCTION

The pathophysiological contribution of FGF-23 in hypophosphatemic diseases was supported by animal studies in which the long-term administration of recombinant fibroblast growth factor-23 reproduced hypophosphatemic rickets with a low serum 1,25-dihydroxyvitamin D [1,25(OH)2D] level. However, there is no clear understanding of how FGF-23 causes these changes.

MATERIALS AND METHODS

To elucidate the molecular mechanisms of the FGF-23 function, we investigated the short-term effects of a single administration of recombinant FGF-23 in normal and parathyroidectmized animals.

RESULTS

An injection of recombinant FGF-23 caused a reduction in serum phosphate and 1,25(OH)2D levels. A decrease in serum phosphate was first observed 9 h after the injection and was accompanied with a reduction in renal mRNA and protein levels for the type IIa sodium-phosphate cotransporter (NaPi-2a). There was no increase in the parathyroid hormone (PTH) level throughout the experiment, and hypophosphatemia was reproduced by FGF-23 in parathyroidectomized rats. Before this hypophosphatemic effect, the serum 1,25(OH)2D level had already descended at 3 h and reached the nadir 9 h after the administration. FGF-23 reduced renal mRNA for 25-hydroxyvitamin D-1alpha-hydroxylase and increased that for 25-hydroxyvitamin D-24-hydroxylase starting at 1 h. In addition, an injection of calcitriol into normal mice increased the serum FGF-23 level within 4 h.

CONCLUSIONS

FGF-23 regulates NaPi-2a independently of PTH and the serum 1,25(OH)2D level by controlling renal expressions of key enzymes of the vitamin D metabolism. In conclusion, FGF-23 is a potent regulator of phosphate and vitamin D homeostasis.

Authors+Show Affiliations

Pharmaceutical Research Laboratories, KIRIN Brewery Co., Ltd., Takasaki, Gumma, Japan. tyamashita@kirin.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15040831

Citation

Shimada, Takashi, et al. "FGF-23 Is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 19, no. 3, 2004, pp. 429-35.
Shimada T, Hasegawa H, Yamazaki Y, et al. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res. 2004;19(3):429-35.
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. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 19(3), 429-35.
Shimada T, et al. FGF-23 Is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis. J Bone Miner Res. 2004;19(3):429-35. PubMed PMID: 15040831.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. AU - Shimada,Takashi, AU - Hasegawa,Hisashi, AU - Yamazaki,Yuji, AU - Muto,Takanori, AU - Hino,Rieko, AU - Takeuchi,Yasuhiro, AU - Fujita,Toshiro, AU - Nakahara,Kazuhiko, AU - Fukumoto,Seiji, AU - Yamashita,Takeyoshi, Y1 - 2003/12/29/ PY - 2003/05/29/received PY - 2003/08/05/revised PY - 2003/10/10/accepted PY - 2004/3/26/pubmed PY - 2004/12/16/medline PY - 2004/3/26/entrez SP - 429 EP - 35 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 19 IS - 3 N2 - UNLABELLED: We analyzed the effects of an FGF-23 injection in vivo. FGF-23 caused a reduction in serum 1,25-dihydroxyvitamin D by altering the expressions of key enzymes for the vitamin D metabolism followed by hypophosphatemia. This study indicates that FGF-23 is a potent regulator of the vitamin D and phosphate metabolism. INTRODUCTION: The pathophysiological contribution of FGF-23 in hypophosphatemic diseases was supported by animal studies in which the long-term administration of recombinant fibroblast growth factor-23 reproduced hypophosphatemic rickets with a low serum 1,25-dihydroxyvitamin D [1,25(OH)2D] level. However, there is no clear understanding of how FGF-23 causes these changes. MATERIALS AND METHODS: To elucidate the molecular mechanisms of the FGF-23 function, we investigated the short-term effects of a single administration of recombinant FGF-23 in normal and parathyroidectmized animals. RESULTS: An injection of recombinant FGF-23 caused a reduction in serum phosphate and 1,25(OH)2D levels. A decrease in serum phosphate was first observed 9 h after the injection and was accompanied with a reduction in renal mRNA and protein levels for the type IIa sodium-phosphate cotransporter (NaPi-2a). There was no increase in the parathyroid hormone (PTH) level throughout the experiment, and hypophosphatemia was reproduced by FGF-23 in parathyroidectomized rats. Before this hypophosphatemic effect, the serum 1,25(OH)2D level had already descended at 3 h and reached the nadir 9 h after the administration. FGF-23 reduced renal mRNA for 25-hydroxyvitamin D-1alpha-hydroxylase and increased that for 25-hydroxyvitamin D-24-hydroxylase starting at 1 h. In addition, an injection of calcitriol into normal mice increased the serum FGF-23 level within 4 h. CONCLUSIONS: FGF-23 regulates NaPi-2a independently of PTH and the serum 1,25(OH)2D level by controlling renal expressions of key enzymes of the vitamin D metabolism. In conclusion, FGF-23 is a potent regulator of phosphate and vitamin D homeostasis. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/15040831/FGF_23_is_a_potent_regulator_of_vitamin_D_metabolism_and_phosphate_homeostasis_ L2 - https://doi.org/10.1359/JBMR.0301264 DB - PRIME DP - Unbound Medicine ER -