PubMed Health⌕ Search

Biomedical subjects

R Brommage

Publications and source records attributed to R Brommage.

43 records · Page 3Linked to original sources

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.

Animals↗

1- but not 24-hydroxylation of vitamin D is required for skeletal mineralization in rats.

To evaluate the importance of 1- and 24-hydroxylation of 25-hydroxyvitamin D3 on skeletal mineralization, male and female rats from vitamin D-deficient mothers were administered from weaning either 100 pmol/day of 25-hydroxyvitamin D3, 50 pmol/day of 1,25-dihydroxyvitamin D3, or 100 pmol/day of 24,24-difluoro-25-hydroxyvitamin D3 as their sole source of vitamin D. A separate group of rats did not receive any vitamin D. 1,25-Dihydroxyvitamin D3 was given by constant infusion at a dose that normalized plasma calcium concentrations and produced normal body weight gains. Skeletal mineralization was studied by determining femur organic and ash weights. Femurs were obtained from male rats 6 wk after weaning, from female rats at conception, at the end of lactation, and 6 wk after lactation, and from weanling pups born to the female rats. No striking differences in femur organic and ash weights were found between 25-hydroxyvitamin D3 groups and either the 1,25-dihydroxyvitamin D3 group or the 24,24-difluoro-25-hydroxyvitamin D3 group, whereas the vitamin D-deficient rats had poorly mineralized femurs. These results indicate that 1,25-dihydroxyvitamin D3 at a lower dose is as fully active as 25-hydroxyvitamin D3 in promoting skeletal mineralization in the rat and that preventing the 24-hydroxylation of 25-hydroxyvitamin D3 by administering 24,24-difluoro-25-hydroxyvitamin D3 does not elicit any obvious skeletal abnormality, especially on mineralization.

Aging↗

Growth failure in vitamin D-deficient rat pups.

Vitamin D-deficient rat pups were produced by feeding normal impregnated rats a diet deficient in vitamin D after mating. The rat pups appeared normal at birth but stopped growing at 1 week of age. Despite this growth failure, these pups were normocalcemic. Analyses of calvaria from a similar group of dams given vitamin D3 showed that these dams mobilized skeletal calcium to meet the calcium requirements of their growing pups.

Animals↗

Passive accumulation of magnesium, sodium, and potassium by chick calvaria.

Four-day-old chick calvaria were used to determine the passive concentrations of magnesium, sodium, and potassium in metabolically poisoned bone. When incubated in buffers containing the blood levels of sodium and magnesium, these calvaria contained sodium and magnesium at the identical concentrations found in freshly dissected calvaria. Calvarial sodium and magnesium levels could be varied by altering the buffer concentrations of these cations. The potassium content of metabolically poisoned calvaria incubated in buffers containing 4 mM potassium was less than 20% of the content of freshly dissected calvaria. When the buffer concentrations of sodium and potassium were systematically varied, ouabain-poisoned calvaria concentrated these cations in the bone extracellular fluid by a factor of approximately two above buffer cation levels. Presumably, the hydroxyapatite crystal zeta potential is responsible for this concentrative phenomenon. These results are discussed in terms of the control of the ionic content of the bone extracellular fluid by the postulated "bone membrane."

Animals↗

The measurement of Ca2+ effluxes from bone.

To facilitate the study of membrane function in the control of the flow of ions into and out of bone, it was desirable to develop a system for the direct quantitation of unidirectional effluxes of calcium and phosphate from bones. Based on a mathematical analysis of the problem, a specially designed Ussing chamber was developed which proved successful. Calvaria from 2-day-old rat pups, 3-day chicks and adult mice were evaluated. Calcium influxes which exceeded the corresponding effluxes were observed in the neonatal calvaria but not with those from adult mice. Also, an asymmetry in efflux was observed in rat calvaria, the inner side of the skull showed a higher efflux than did the external side. No such asymmetry was seen with calvaria from chicks or mice. This new technology should permit a further exploration of the role of the bone membrane in electrolyte homeostasis.

Animals↗