Renal effect of vitamin D metabolites: evidence for the essential role of the 25(OH) group.

Abstract

The effects of 1 alpha (OH)vitamin D3 [1 alpha (OH)D3] and 24,25(OH)2vitamin D3 [24,25(OH)2D3] on the phosphaturic action of parathyroid hormone (PTH) were studied in two groups of parathyroidectomized (PTX) rats. In group 1, PTX PTH-infused rats received intravenous 1 alpha (OH)D3, and in group 2, PTX PTH-infused rats received intravenous 24,25(OH)2D3. PTX PTH-infused rats served as controls. The effects of both vitamin D metabolites on renal PTH-activated adenylate cyclase (AC) were studied in vitro. In group 1, PTH increased fractional excretion of phosphate (CP/CIn) from 0.045 +/- 0.012 (+/- SE) to 0.263 +/- 0.011 (P less than 0.005). 1 alpha (OH)D3 failed to influence this response. In group 2, PTH increased CP/CIn from 0.055 +/- 0.008 to 0.289 +/- 0.027 (P less than 0.005). 24,25(OH)2D3 reduced the PTH-induced rise in CP/CIn from 0.289 +/- 0.027 to 0.192 +/- 0.021 (P less than 0.01) and decreased the urinary excretion of adenosine 3',5'-cyclic monophosphate. In vitro, 24,25(OH)2D3 blunted the PTH-activated AC, whereas 1 alpha (OH)D3 had no effect. These results show that 24,25(OH)D3, similar to two other 25(OH) metabolites of vitamin D-25(OH)vitamin D3 and 1,25(OH)2vitamin D3-suppresses the phosphaturic action of PTH, whereas 1 alpha(OH)D3, which is devoid of a 25(OH) group, lacks this effect. This suggests that a 25(OH) group is a prerequisite for the antiphosphaturic effect of vitamin D, whereas the 1 alpha (OH) group is not essential for this action.