24-24-difluoro-25-hydroxyvitamin-d3 and Body-Weight

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.

Topics: Animals; Body Weight; Calcifediol; Calcitriol; Calcium; Estrus; Female; Hydroxylation; Pregnancy; Rats; Sexual Maturation; Structure-Activity Relationship; Vitamin D Deficiency

The biological activity of subcutaneously injected 24,24-difluoro-25-hydroxycholecalciferol was compared with that of 25-hydroxycholecalciferol in the vitamin D-deficient growing chick. 24,24-Difluoro-25-hydroxycholecalciferol is equal to 25-hydroxycholecalciferol in the stimulation of: 1) growth, 2) intestinal calcium absorption, 3) elevation of serum calcium and serum phosphorus, 4) healing of rachitic cartilage (radiography), and 5) mineralization of rachitic bone (bone ash). The response appears to be linear in the range of 13.0 to 325 pmol daily. Since 24,24-difluorocholecaliferol cannot be 24-hydroxylated to produce either 24,25-dihydroxycholecalciferol or 1,24,25-trihydroxycholecalciferol, while it can be 1 alpha-hydroxylated to produce 24,24-difluoro-1,25-dihydroxycholecalciferol, these results demonstrate that 24-hydroxylation is not required for the known functions of cholecalciferol in the chick.

Topics: Animals; Body Weight; Bone and Bones; Calcifediol; Calcium; Chickens; Dose-Response Relationship, Drug; Male; Phosphorus; Structure-Activity Relationship; Vitamin D Deficiency

Topics: Animals; Body Weight; Bone and Bones; Calcifediol; Cholecalciferol; Femur; Hydroxycholecalciferols; Male; Minerals; Rats; Vitamin D Deficiency