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Dietary Phosphate Deprivation Increases Renal Synthesis and Decreases Renal Catabolism of 1,25-Dihydroxycholecalciferol in Guinea Pigs^{1, 2,}

Departments of Biochemistry and Medicine, Queen's University, Kingston, ON, Canada K7L 3N6

In guinea pigs, dietary phosphate deprivation decreases plasma phosphate concentration, increases plasma 1,25-dihydroxycholecalciferol [1,25-(OH)₂D₃] concentration and causes hypercalcemia concurrent with the maximal increase in plasma 1,25-(OH)₂D₃ levels. Our objective was to determine whether increased synthesis or decreased catabolism contributed to the elevation in plasma 1,25-(OH)₂D₃. Preliminary experiments using renal mitochondria from guinea pigs fed a control diet revealed that 23,25-dihydroxycholecalciferol [23,25-(OH)₂D₃], not 24,25-dihydroxycholecalciferol [24,25-(OH)₂D₃], was the reciprocal side-chain metabolite to 1,25-(OH)₂D₃ in this species. An assay employing guinea pig renal mitochondria was used to measure the renal synthesis of 1,25-(OH)₂D₃ and 23,25-(OH)₂D₃ from [³H]25-OH-D₃. These metabolites were unequivocally identified by combinations of HPLC, ultraviolet spectrophotometry and mass spectrometry. This renal mitochondrial assay was subsequently used to investigate the effect of dietary phosphate deprivation on guinea pig vitamin D metabolism. Within 1 wk the rate of synthesis of 1,25-(OH)₂D₃ was maximal in phosphate-deprived guinea pigs. This rate was significantly (P < 0.005) higher than that achieved in same-day control guinea pigs. Conversely, within 1 d the synthesis of 23,25-(OH)₂D₃ was significantly (P < 0.005) decreased in phosphate-deprived guinea pigs. Similarly, the rate of 1,25-(OH)₂D₃ metabolism was decreased within 1 d of dietary phosphate deprivation and was at a minimum within 1 wk. This rate was significantly (P < 0.005) less than that attained in same-day control guinea pigs. These results suggest that both increased synthesis and decreased metabolism of 1,25-(OH)₂D₃ contribute to the plasma 1,25-(OH)₂D₃ elevation that occurs in response to dietary phosphate deprivation.

KEY WORDS: • phosphate • 1,25-dihydroxycholecalciferol • renal mitochondria • metabolism • guinea pigs

¹ Presented in part at the Annual Meeting of the Canadian Federation of Biological Societies, June 15–18, 1988 at Laval University, Québec City, PQ, Canada. [Simboli, M. & Jones, G. (1988) Regulation of renal 25-hydroxy vitamin D₃ metabolism by dietary phosphate deprivation. (abs. 664)]

² Supported by a grant from the Medical Research Council of Canada (MA 9475 to GJ).

³ Present address: Department of Biochemistry, University of Ottawa, Ottawa, ON, Canada K1H 8M5.

⁴ To whom reprint requests should be addressed.

Manuscript received 17 January 1991. Revision accepted 16 April 1991.

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