24,25(OH) 2 D 3 Enhances the Calcemic Effect of 1,25(OH) 2 D 3

Abstract

Abstract

The effect of 24,25(OH)₂D₃ on 1,25(OH)₂D₃-induced hypercalcemia was studied in normal rats. Serum (S) levels and urinary excretion of Ca²⁺ (U_caV) were measured in (a) control rats, (b) rats receiving a daily sc injection of 54 ng 1,25(OH)₂D₃, (c) rats receiving 24,25(OH)₂D₃ in the same dose and same manner, and (d) rats receiving 1,25(OH)₂D₃ + 24,25(OH)₂D₃. The animals were housed in metabolic cages and 24-hr urine specimens were collected. After 24 hr SCa²⁺ increased similarly with 1,25(OH)₂D₃ and with 1,25(OH)₂D₃ + 24,25(OH)₂D₃, while 24,25(OH)₂D₃ alone did not change SCa²⁺. U_caV after 24 hr increased significantly less (P < 0.025) with 1,25(OH)₂D₃ + 24,25(OH)₂D₃ than with 1,25(OH)₂D₃ alone. After 5 days of 1,25(OH)₂D₃, SCa²⁺ rose from 5.1 ± 0.15 to 6.29 ± 0.08 whereas 1,25(OH)₂D₃ + 24,25(OH)₂D₃ effected a greater increase in SCa²⁺ up to 6.63 ± 0.09 (P < 0.01). 24,25(OH)₂D₃ alone did not change SCa²⁺. U_CaV after 5 days of treatment rose similarly with 1,25(OH)₂D₃ and with 1,25(OH)₂D₃ + 24,25(OH)₂D₃. After 10 days of 1,25(OH)₂D₃ SCa²⁺ was 6.17 ± 0.15 meq/liter while with the combination SCa²⁺ rose to 6.74 ± 0.2 (P < 0.025). 24,25(OH)₂D₃ alone did not change SCa²⁺. These results show that (a) 24,25(OH)₂D₃ alone does not alter SCa²⁺ in normal rats, (b) combined administration of 1,25(OH)₂D₃ + 24,25(OH)₂D₃ enhances the hypercalcemic response to 1,25(OH)₂D₃ without a parallel increase in U_CaV, and (c) it is suggested that the effect of 24,25(OH)₂D₃ on serum Ca²⁺ level, at least partly, may result from its hypocalciuric effect.