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Changes in specific dexamethasone binding during aging in WI-38 cells

B A Rosner, V J Cristofalo

    Endocrinology
    |May 1, 1981
    PubMed
    Summary
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    Aging WI-38 cells show decreased glucocorticoid binding sites, explaining reduced responsiveness. This study identifies specific dexamethasone (DEX) binding sites and their decline with cellular aging.

    Area of Science:

    • Cell Biology
    • Endocrinology
    • Gerontology

    Background:

    • Normal human diploid cell line WI-38 exhibits increased proliferation with glucocorticoids.
    • Glucocorticoids play a crucial role in cellular processes and their efficacy can change with age.

    Purpose of the Study:

    • To investigate the presence and characteristics of glucocorticoid binding sites in WI-38 cells.
    • To determine how the number and affinity of these binding sites change with cellular aging.
    • To correlate glucocorticoid binding with cellular proliferation in aging cells.

    Main Methods:

    • Hormone binding studies using radiolabeled dexamethasone ([3H]DEX) in intact WI-38 cell monolayers.
    • Competition studies with unlabeled steroids to assess molecular specificity.

    Related Experiment Videos

  • Quantification of binding sites and affinity in cells of varying ages in vitro.

    • Main Results:

    • WI-38 cells possess high-affinity binding sites for dexamethasone (DEX) and hydrocortisone.
    • Specific DEX binding sites decreased by 40% in aged WI-38 cells without significant change in affinity.
    • Steroid competition studies confirmed molecular specificity and a correlation between binding and proliferation.

    Conclusions:

    • The decrease in specific glucocorticoid binding sites with cellular aging may explain the reduced responsiveness of WI-38 cells to these hormones.
    • Findings in WI-38 cells mirror observations in aged animal tissues, suggesting a conserved aging mechanism.
    • This research provides insight into the molecular basis of age-related changes in hormone sensitivity.