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. 1989 May;83(5):1494–1499. doi: 10.1172/JCI114043

Physiologic regulation of the serum concentration of 1,25-dihydroxyvitamin D by phosphorus in normal men.

A A Portale 1, B P Halloran 1, R C Morris Jr 1
PMCID: PMC303852  PMID: 2708521

Abstract

We asked this question: in normal humans, is either a normal dietary intake or normal serum concentration of phosphorus a determinant of the serum concentration of 1,25(OH)2D? In seven normal men whose dietary phosphorus was decreased from 2,300 to 625 mg/d, each intake for 8-9 d, under strictly controlled, normal metabolic conditions, we measured serum concentrations of 1,25(OH)2D daily, and concentrations of phosphorus hourly throughout a 24-h period, before and after restriction. Decreasing dietary phosphorus induced: (a) a 58% increase in serum levels of 1,25(OH)2D; (b) a 35% decrease in serum levels of phosphorus measured in the afternoon; (c) a 12% decrease in the 24-h mean serum level of phosphorus; but, (d) no decrease in morning fasting levels of phosphorus. Serum concentrations of 1,25(OH)2D varied inversely and significantly with 24-h mean concentrations of phosphorus (r = -0.77, P less than 0.001). When these data are combined with those of our prior study in which dietary phosphorus was varied over an extreme range, the relationship between serum levels of 1,25(OH)2D and 24-h mean serum levels of phosphorus is even stronger (r = -0.90, P less than 0.001). In the aggregate, the results demonstrate that in normal men, dietary phosphorus throughout a normal range and beyond, can finely regulate the renal production and serum concentration of 1,25(OH)2D, and provide evidence that this regulation is mediated by fine modulation of the serum concentration of phosphorus.

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Selected References

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  1. Akiba T., Endou H., Koseki C., Sakai F., Horiuchi N., Suda T. Localization of 25-hydroxyvitamin D3-1 alpha-hydroxylase activity in the mammalian kidney. Biochem Biophys Res Commun. 1980 May 14;94(1):313–318. doi: 10.1016/s0006-291x(80)80222-1. [DOI] [PubMed] [Google Scholar]
  2. Armbrecht H. J., Wongsurawat N., Zenser T. V., Davis B. B. Effect of PTH and 1,25(OH)2D3 on renal 25(OH)D3 metabolism, adenylate cyclase, and protein kinase. Am J Physiol. 1984 Jan;246(1 Pt 1):E102–E107. doi: 10.1152/ajpendo.1984.246.1.E102. [DOI] [PubMed] [Google Scholar]
  3. Baxter L. A., DeLuca H. F. Stimulation of 25-hydroxyvitamin D3-1alpha-hydroxylase by phosphate depletion. J Biol Chem. 1976 May 25;251(10):3158–3161. [PubMed] [Google Scholar]
  4. Biber J., Murer H. Na-Pi cotransport in LLC-PK1 cells: fast adaptive response to Pi deprivation. Am J Physiol. 1985 Nov;249(5 Pt 1):C430–C434. doi: 10.1152/ajpcell.1985.249.5.C430. [DOI] [PubMed] [Google Scholar]
  5. Bikle D. D., Rasmussen H. The ionic control of 1,25-dihydroxyvitamin D3 production in isolated chick renal tubules. J Clin Invest. 1975 Feb;55(2):292–298. doi: 10.1172/JCI107932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Booth B. E., Tsai H. C., Morris R. C., Jr Parathyroidectomy reduces 25-hydroxyvitamin D3-1 alpha-hydroxylase activity in the hypocalcemic vitamin D-deficient chick. J Clin Invest. 1977 Dec;60(6):1314–1320. doi: 10.1172/JCI108890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Booth B. E., Tsai H. C., Morris R. C., Jr Vitamin D status regulates 25-hydroxyvitamin D3-1 alpha-hydroxylase and its responsiveness to parathyroid hormone in the chick. J Clin Invest. 1985 Jan;75(1):155–161. doi: 10.1172/JCI111668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Broadus A. E., Magee J. S., Mallette L. E., Horst R. L., Lang R., Jensen P. S., Gertner J. M., Baron R. A detailed evaluation of oral phosphate therapy in selected patients with primary hyperparathyroidism. J Clin Endocrinol Metab. 1983 May;56(5):953–961. doi: 10.1210/jcem-56-5-953. [DOI] [PubMed] [Google Scholar]
  9. Brunette M. G., Chan M., Ferriere C., Roberts K. D. Site of 1,25(OH)2 vitamin D3 synthesis in the kidney. Nature. 1978 Nov 16;276(5685):287–289. doi: 10.1038/276287a0. [DOI] [PubMed] [Google Scholar]
  10. Calvo M. S., Kumar R., Heath H., 3rd Elevated secretion and action of serum parathyroid hormone in young adults consuming high phosphorus, low calcium diets assembled from common foods. J Clin Endocrinol Metab. 1988 Apr;66(4):823–829. doi: 10.1210/jcem-66-4-823. [DOI] [PubMed] [Google Scholar]
  11. Caverzasio J., Brown C. D., Biber J., Bonjour J. P., Murer H. Adaptation of phosphate transport in phosphate-deprived LLC-PK1 cells. Am J Physiol. 1985 Jan;248(1 Pt 2):F122–F127. doi: 10.1152/ajprenal.1985.248.1.F122. [DOI] [PubMed] [Google Scholar]
  12. Colston K. W., Evans I. M., Galante L., MacIntyre I., Moss D. W. Regulation of vitamin D metabolism: factors influencing the rate of formation of 1,25-dihydroxycholecalciferol by kidney homogenates. Biochem J. 1973 Jul;134(3):817–820. [PMC free article] [PubMed] [Google Scholar]
  13. Fraser D. R., Kodicek E. Regulation of 25-hydroxycholecalciferol-1-hydroxylase activity in kidney by parathyroid hormone. Nat New Biol. 1973 Feb 7;241(110):163–166. doi: 10.1038/newbio241163a0. [DOI] [PubMed] [Google Scholar]
  14. Fraser D. R., Kodicek E. Unique biosynthesis by kidney of a biological active vitamin D metabolite. Nature. 1970 Nov 21;228(5273):764–766. doi: 10.1038/228764a0. [DOI] [PubMed] [Google Scholar]
  15. Garabedian M., Holick M. F., Deluca H. F., Boyle I. T. Control of 25-hydroxycholecalciferol metabolism by parathyroid glands. Proc Natl Acad Sci U S A. 1972 Jul;69(7):1673–1676. doi: 10.1073/pnas.69.7.1673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gray R. W., Napoli J. L. Dietary phosphate deprivation increases 1,25-dihyroxyvitamin D3 synthesis in rat kidney in vitro. J Biol Chem. 1983 Jan 25;258(2):1152–1155. [PubMed] [Google Scholar]
  17. Gray R. W., Omdahl J. L., Ghazarian J. G., DeLuca H. F. 25-Hydroxycholecalciferol-1-hydroxylase. Subcellular location and properties. J Biol Chem. 1972 Dec 10;247(23):7528–7532. [PubMed] [Google Scholar]
  18. Gray R. W., Wilz D. R., Caldas A. E., Lemann J., Jr The importance of phosphate in regulating plasma 1,25-(OH)2-vitamin D levels in humans: studies in healthy subjects in calcium-stone formers and in patients with primary hyperparathyroidism. J Clin Endocrinol Metab. 1977 Aug;45(2):299–306. doi: 10.1210/jcem-45-2-299. [DOI] [PubMed] [Google Scholar]
  19. Gray R., Boyle I., DeLuca H. F. Vitamin D metabolism: the role of kidney tissue. Science. 1971 Jun 18;172(3989):1232–1234. doi: 10.1126/science.172.3989.1232. [DOI] [PubMed] [Google Scholar]
  20. Henry H. L., Midgett R. J., Norman A. W. Regulation of 25-hydroxyvitamin D3-1-hydroxylase in vivo. J Biol Chem. 1974 Dec 10;249(23):7584–7592. [PubMed] [Google Scholar]
  21. Henry H. L. Regulation of the hydroxylation of 25-hydroxyvitamin D3 in vivo and in primary cultures of chick kidney cells. J Biol Chem. 1979 Apr 25;254(8):2722–2729. [PubMed] [Google Scholar]
  22. Insogna K. L., Broadus A. E., Gertner J. M. Impaired phosphorus conservation and 1,25 dihydroxyvitamin D generation during phosphorus deprivation in familial hypophosphatemic rickets. J Clin Invest. 1983 Jun;71(6):1562–1569. doi: 10.1172/JCI110912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kawashima H., Torikai S., Kurokawa K. Localization of 25-hydroxyvitamin D3 1 alpha-hydroxylase and 24-hydroxylase along the rat nephron. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1199–1203. doi: 10.1073/pnas.78.2.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lufkin E. G., Kumar R., Heath H., 3rd Hyperphosphatemic tumoral calcinosis: effects of phosphate depletion on vitamin D metabolism, and of acute hypocalcemia on parathyroid hormone secretion and action. J Clin Endocrinol Metab. 1983 Jun;56(6):1319–1322. doi: 10.1210/jcem-56-6-1319. [DOI] [PubMed] [Google Scholar]
  25. Maierhofer W. J., Gray R. W., Lemann J., Jr Phosphate deprivation increases serum 1,25-(OH)2-vitamin D concentrations in healthy men. Kidney Int. 1984 Mar;25(3):571–575. doi: 10.1038/ki.1984.56. [DOI] [PubMed] [Google Scholar]
  26. Midgett R. J., Spielvogel A. M., Coburn J. W., Norman A. W. Studies on calciferol metabolism. VII. The renal production of the biologically active form of vitamin D, 1,25-dihydroxycholecalciferol; species, tissue and subcellular distribution. J Clin Endocrinol Metab. 1973 Jun;36(6):1153–1161. doi: 10.1210/jcem-36-6-1153. [DOI] [PubMed] [Google Scholar]
  27. Portale A. A., Booth B. E., Halloran B. P., Morris R. C., Jr Effect of dietary phosphorus on circulating concentrations of 1,25-dihydroxyvitamin D and immunoreactive parathyroid hormone in children with moderate renal insufficiency. J Clin Invest. 1984 Jun;73(6):1580–1589. doi: 10.1172/JCI111365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Portale A. A., Halloran B. P., Morris R. C., Jr Dietary intake of phosphorus modulates the circadian rhythm in serum concentration of phosphorus. Implications for the renal production of 1,25-dihydroxyvitamin D. J Clin Invest. 1987 Oct;80(4):1147–1154. doi: 10.1172/JCI113172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Portale A. A., Halloran B. P., Murphy M. M., Morris R. C., Jr Oral intake of phosphorus can determine the serum concentration of 1,25-dihydroxyvitamin D by determining its production rate in humans. J Clin Invest. 1986 Jan;77(1):7–12. doi: 10.1172/JCI112304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Shepard R. M., Horst R. L., Hamstra A. J., DeLuca H. F. Determination of vitamin D and its metabolites in plasma from normal and anephric man. Biochem J. 1979 Jul 15;182(1):55–69. doi: 10.1042/bj1820055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tanaka Y., DeLuca H. F. Rat renal 25-hydroxyvitamin D3 1- and 24-hydroxylases: their in vivo regulation. Am J Physiol. 1984 Feb;246(2 Pt 1):E168–E173. doi: 10.1152/ajpendo.1984.246.2.E168. [DOI] [PubMed] [Google Scholar]
  32. Tanaka Y., Deluca H. F. The control of 25-hydroxyvitamin D metabolism by inorganic phosphorus. Arch Biochem Biophys. 1973 Feb;154(2):566–574. doi: 10.1016/0003-9861(73)90010-6. [DOI] [PubMed] [Google Scholar]
  33. Tieder M., Modai D., Samuel R., Arie R., Halabe A., Bab I., Gabizon D., Liberman U. A. Hereditary hypophosphatemic rickets with hypercalciuria. N Engl J Med. 1985 Mar 7;312(10):611–617. doi: 10.1056/NEJM198503073121003. [DOI] [PubMed] [Google Scholar]
  34. Trechsel U., Bonjour J. P., Fleisch H. Regulation of the metabolism of 25-hydroxyvitamin D3 in primary cultures of chick kidney cells. J Clin Invest. 1979 Jul;64(1):206–217. doi: 10.1172/JCI109441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Van Cauter E. Method for characterization of 24-h temporal variation of blood components. Am J Physiol. 1979 Sep;237(3):E255–E264. doi: 10.1152/ajpendo.1979.237.3.E255. [DOI] [PubMed] [Google Scholar]
  36. Van Den Berg C. J., Kumar R., Wilson D. M., Heath H., 3rd, Smith L. H. Orthophosphate therapy decreases urinary calcium excretion and serum 1,25-dihydroxyvitamin D concentrations in idiopathic hypercalciuria. J Clin Endocrinol Metab. 1980 Nov;51(5):998–1001. doi: 10.1210/jcem-51-5-998. [DOI] [PubMed] [Google Scholar]

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