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Vitamin D: recent advances.

H F DeLuca, H K Schnoes

    Annual Review of Biochemistry
    |January 1, 1983
    PubMed
    Summary
    This summary is machine-generated.

    Research reveals new vitamin D functions and metabolism pathways. Nuclear localization of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) in various tissues suggests subtle roles, and its potential link to cancer is explored.

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    A new, highly sensitive assay for 1,25-dihydroxyvitamin D not requiring high-performance liquid chromatography: application of monoclonal antibody against vitamin D receptor to radioreceptor assay.

    Analytical biochemistry·1992

    Area of Science:

    • Endocrinology
    • Molecular Biology
    • Biochemistry

    Background:

    • Vitamin D metabolism and mechanism of action research is highly active.
    • Specific nuclear localization of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) has been observed in target organs and other tissues.
    • A receptor for 1,25-(OH)2D3 has been identified in cells and cancer cell lines, suggesting a potential link between the vitamin D system and cancer.

    Purpose of the Study:

    • To explore novel functions and metabolic pathways of vitamin D.
    • To investigate the mechanism of action of 1,25-(OH)2D3, including its nuclear-mediated processes.
    • To examine the role of vitamin D in cellular differentiation and its potential relationship with cancer.

    Main Methods:

    • Autoradiography to track the nuclear localization of 1,25-(OH)2D3.

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  • Identification of a macromolecule (receptor) that specifically binds 1,25-(OH)2D3.
  • Biochemical analysis of vitamin D metabolism enzymes, including 1 alpha-hydroxylase and 25-hydroxylase.
  • Synthesis and testing of novel vitamin D analogs.

    • Main Results:

    • Specific nuclear localization of 1,25-(OH)2D3 was demonstrated in various tissues, indicating previously unappreciated functions.
    • A potential relationship between the vitamin D system and cancer was suggested by the presence of the 1,25-(OH)2D3 receptor in tumor cell lines and its effect on myeloid leukemia cells.
    • Advances in understanding vitamin D metabolism include the identification of 1 alpha-hydroxylase in the placenta and the characterization of renal and hepatic hydroxylases.
    • New metabolic pathways, such as 23-oxidation and lactone formation, were identified, although their products showed low biological activity.
    • Novel vitamin D analogs, including fluorinated metabolites, were synthesized and demonstrated that 24-hydroxylation, 26-hydroxylation, and lactone formation are not critical for vitamin D function.
    • 1-hydroxy analogs of vitamin D metabolites proved to be significantly more potent than 1,25-(OH)2D3.

    Conclusions:

    • Vitamin D possesses subtle functions in various tissues beyond its classical roles.
    • The vitamin D system may be implicated in cancer development or progression.
    • Significant progress has been made in elucidating vitamin D metabolism, including enzyme characterization and the discovery of new pathways.
    • Novel vitamin D analogs offer powerful tools for understanding vitamin D's mechanism of action and may lead to new therapeutic agents.