Endocrinology, Vol 120, 609-616, Copyright © 1987 by Endocrine Society

ARTICLES

Effect of the X-linked Hyp mutation and vitamin D status on induction of renal 25-hydroxyvitamin D3-24-hydroxylase

HS Tenenhouse and G Jones

The present study was undertaken to evaluate the response of Hyp mice to regulators known to inhibit renal 25-hydroxyvitamin D3-1-hydroxylase (1-hydroxylase) and stimulate renal 25-hydroxyvitamin D-24-hydroxylase (24-hydroxylase). Renal mitochondrial metabolism of 25-hydroxyvitamin D3 (25OHD3) was initially examined in vitamin D- and calcium-deprived normal and mutant mice (with no detectable 24-hydroxylase) treated with either calcium, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], or both calcium + 1,25-(OH)2D3. In normal mice, 1,25-(OH)2D3 treatment was more effective than calcium in turning off 1-hydroxylase and turning on 24- hydroxylase activity; serum calcium, however, was similarly increased by both treatments. Although calcium + 1,25-(OH)2D3 did not result in a further change in 25OHD3 metabolism in normal mice, a further elevation in serum calcium was apparent. In Hyp mice, treatment with calcium + 1,25-(OH)2D3 resulted in a greater decrease in 1-hydroxylase and a greater increase in 24-hydroxylase and in serum calcium than treatment with either agent alone. In spite of similar serum calcium levels in both genotypes, 24-hydroxylase was 20-fold, 3-fold, and 8-fold greater in Hyp mice relative to normals treated with calcium, 1,25-(OH)2D3, and calcium + 1,25-(OH)2D3, respectively. Kinetic studies revealed that the maximum velocity (Vmax) for induced 24-hydroxylase was 6-fold greater than normal in Hyp mice whereas the apparent Michaelis-Menten constant (Km) was not different in the two groups of calcium + 1,25-(OH)2D3- treated mice. The effect of 1,25-(OH)2D3 treatment on the above serum and renal parameters was also examined in vitamin D replete normal and Hyp mice. A sharp rise in serum phosphate was observed in 1,25-(OH)2D3- treated Hyp mice whereas normal littermates experienced marked hypercalcemia in response to treatment. Renal 24-hydroxylase was significantly stimulated by 1,25-(OH)2D3 treatment in both normal and Hyp mice and genotype differences were not apparent. The present study demonstrates that vitamin D- and calcium-deprived Hyp mice are more responsive to signals which induce 24-hydroxylase than normal littermates; Vmax for induced 24-hydroxylase is 6-fold greater in Hyp mice than in normal littermates whereas apparent Km is unchanged; the inhibitory control of 1-hydroxylase appears to be intact in the mutant strain; induced 24-hydroxylase is similar in vitamin D replete normal and Hyp mice; and vitamin D status can thus modify the response of both genotypes to treatment with 1,25-(OH)2D3.(ABSTRACT TRUNCATED AT 400 WORDS)

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				M. H. Meyer, E. Dulde, and R. A. Meyer Jr. The genomic response of the mouse kidney to low-phosphate diet is altered in X-linked hypophosphatemia Physiol Genomics, June 17, 2004; 18(1): 4 - 11. [Abstract] [Full Text] [PDF]