24-Hydroxylase: potential key regulator in hypervitaminosis D3 in growing dogs

A group of growing dogs supplemented with cholecalciferol (vitamin D3; HVitD) was studied vs. a control group (CVitD; 54,000 vs. 470 IU vitamin D3/kg diet, respectively) from 3 to 21 wk of age. There were no differences in plasma levels of Pi and growth-regulating hormones between groups and no signs of vitamin D3 intoxication in HVitD. For the duration of the study in HVitD vs. CVitD, plasma 25-hydroxycholecalciferol levels increased 30- to 75-fold; plasma 24,25-dihydroxycholecalciferol levels increased 12- to 16-fold and were accompanied by increased renal 24-hydroxylase gene expression, indicating increased renal 24-hydroxylase activity. Although the synthesis of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] was increased in HVitD vs. CVitD (demonstrated by [3H]1,25(OH)2D3 and increased renal 1α-hydroxylase gene expression), plasma 1,25(OH)2D3 levels decreased by 40% as a result of the even more increased metabolic clearance of 1,25(OH)2D3 (demonstrated by [3H]1,25(OH)2D3 and increased gene expression of...