1- but not 24-hydroxylation of vitamin D is required for growth and reproduction in rats

This study examines whether 1,25-dihydroxyvitamin D3 or 24,24-difluoro-25-hydroxyvitamin D3, an analogue of 25-hydroxyvitamin D3 blocked from undergoing 24-hydroxylation, can maintain normal growth and reproduction in the female rat. Vitamin D-deficient weanling rats were maintained from weaning through mating, pregnancy, and lactation with either 1,25-dihydroxyvitamin D3 (given by continuous subcutaneous infusion), 24,24-difluoro-25-hydroxyvitamin D3, 25-hydroxyvitamin D3, or vehicle. Body weight, plasma calcium levels, estrous cycling time, ability to give birth to live pups, litter weight, number of pups per litter, dam plasma calcium level during lactation, and pup growth to 9 wk of age were recorded. No striking differences were observed between the 25-hydroxyvitamin D3 groups and either the 1,25-dihydroxyvitamin D3 group or the 24,24-difluoro-25-hydroxyvitamin D3 group. However, significant differences in most parameters were observed between the vitamin D-deficient and metabolite- or analogue-dosed rats. The results demonstrate that 1,25-dihydroxyvitamin D3 and/or one of its metabolites is sufficient to maintain normal growth, development, and reproductive functions in the female rat. Because 24,24-difluoro-25-hydroxyvitamin D3 cannot be hydroxylated at C-24, the 24-hydroxylation of 25-hydroxyvitamin D3 is not essential for normal growth, development, and reproduction in the female rat.