• Haussler, Mark R (PI)

Project: Research project

Grant Details


1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is the accepted hormonal form of
vitamin D which facilitates calcium and phosphorus homeostasis by acting on
intestinal mineral absorption and bone remodeling. Recent evidence also
implicates 1,25(OH)2D3 in normal hematopoiesis and cell differentiation.
The proposed study will focus on elucidating the biochemical mechanism of
1,25(OH)2D3 action in a variety of target cells. Using monoclonal antibody
we plan to further characterize the molecular properties of the
1,25(OH)2D3 receptor protein and prove that it is an obligatory mediator of
the hormone's action. We will also study receptor modulation during target
cell differentiation and analyze its binding to putative promotor regions
of vitamin D regulated genes. The functions of 1,25(OH)2D3 in bone will be
examined at the level of differentiating chondrocytes, osteoblasts, and
osteoclast precursor cells. Another biological action of 1,25(OH)2D3, the
induction of its catabolism via C-24 oxidation, will be investigated in
cultured kidney cells. Biochemical details of the hormone's functions
which may involve intracellular calcium and protein kinase C as well as
nuclear protein modification and altered gene expression will be
delineated. Finally, we will probe the regulation of cell growth and
differentiation in normal and tumor cells by 1,25(OH)2D3. These basic
studies will be complemented with measurements of 1,25(OH)2D3 receptor
levels in patients with crush fracture osteoporosis, idiopathic
hypercalciuria, osteogenic sarcoma and myelogenous leukemia. Our findings
should not only reveal some of the early molecular events in the action of
vitamin D, but they may add to our understanding of the pathophysiology and
treatment of metabolic and malignant bone diseases.
Effective start/end date1/1/7512/31/89


  • National Institutes of Health


  • Medicine(all)


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