Biological activity of 1,25-dihydroxyvitamin D₂ and 24-epi-1,25-dihydroxyvitamin D₂

The biological activity of 1,25-dihydroxyvitamin D₂ [1,25(OH)₂D₂] and 24-epi-1,25-dihydroxyvitamin D₂ [24-epi-1,25(OH)₂D₂] has been determined in vitamin D-deficient rats. The biological effectiveness of 1,25(OH)₂D₂ is equal to that reported previously for 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] (15) in intestinal calcium transport, mineralization of bone, mobilization of bone calcium, and elevation of plasma inorganic phosphorus of rachitic rats. However, 24-epi-1,25(OH)₂D₂ is at best one-half as active as 1,25(OH)₂D₂ in stimulating intestinal calcium transport and in the mineralization of rachitic bone. The 24-epi-1,25(OH)₂D₂ is one-third as active as 1,25(OH)₂D₃ in binding to the chick intestinal receptor for 1,25(OH)₂D₃. Thus receptor discrimination may account for the twofold difference in intestinal calcium transport activity. 24-Epi-1,25(OH)₂D₂ appeared inactive in in vivo mobilization of bone calcium or bone phosphorus. On the other hand, in fetal rat bone in culture, the epi compound was only five times less active than 1,25(OH)₂D₂ in inducing resorption. Short-term experiments on bone mineral mobilization in vivo show that the 24-epi-1,25(OH)₂D₂ does induce bone calcium mobilization but that its activity in this respect is short lived. It is suggested that 24-epi-1,25(OH)₂D₂ is more rapidly degraded in vivo than 1,25(OH)₂D₂, and, as a result, it shows preferential activity on intestine whose response to a single dose of 1,25(OH)₂D₂ remains for several days, whereas the short-lived bone system does not remain stimulated during the 24-h period between doses.