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Developmental changes in responsiveness to vitamin D metabolites.
Journal of Steroid Biochemistry
|January 1, 1987
Summary
Vitamin D metabolites 24,25-dihydroxy vitamin D3 and 1,25-dihydroxy vitamin D3 show distinct receptor specificities in developing bone and kidney cells. 24,25(OH)2D3 appears to act as a maturation factor, potentially inducing 1,25(OH)2D3 receptor development.
Area of Science:
- Endocrinology
- Developmental Biology
- Cell Biology
Background:
- Vitamin D is crucial for calcium homeostasis and bone health.
- Different dihydroxy vitamin D metabolites (1,25(OH)2D3 and 24,25(OH)2D3) exist with potentially distinct roles.
- Cellular responsiveness to vitamin D metabolites changes during development.
Purpose of the Study:
- To investigate the specific receptors for 24,25(OH)2D3 and 1,25(OH)2D3 in various developing tissues.
- To characterize the developmental changes in tissue responsiveness to these vitamin D metabolites.
- To explore the potential role of 24,25(OH)2D3 in regulating the development of 1,25(OH)2D3 responsiveness.
Main Methods:
- Analysis of specific vitamin D metabolite receptors in epiphyseal chondroblasts, diaphyseal osteoblasts, and kidney cells from rats and rabbits at different developmental stages.
- Assessment of DNA synthesis and creatine kinase (CKBB) activity in response to vitamin D metabolites.
- In vitro studies using primary kidney cell cultures to examine developmental patterns and the effects of chronic metabolite treatment.
Main Results:
- Epiphyseal chondroblasts possess 24,25(OH)2D3 receptors, while diaphyseal osteoblasts have 1,25(OH)2D3 receptors.
- Kidney responsiveness to vitamin D metabolites shifts from 24,25(OH)2D3 in early development to 1,25(OH)2D3 in mature stages.
- Skeletal and non-skeletal tissues exhibit varied developmental patterns of responsiveness, with some tissues showing a transition from 24,25(OH)2D3 to 1,25(OH)2D3 sensitivity.
- Chronic exposure to 24,25(OH)2D3 in vitro induced precocious development of 1,25(OH)2D3 responsiveness in kidney cells.
Conclusions:
- Specific vitamin D metabolite receptors are differentially expressed in distinct cell types and change during development.
- 24,25(OH)2D3 may function as a developmental maturation factor, potentially by inducing 1,25(OH)2D3 receptors and down-regulating its own receptors.
- These findings highlight the complex, stage-specific roles of vitamin D metabolites in skeletal and non-skeletal tissue development.