Changes in Specific Dexamethasone Binding during Aging in WI-38 Cells*

Abstract

Normal human diploid cell line WI-38, which shows enhanced proliferation in the presence of glucocorticoids, was found to contain high affinity binding sites for dexamethasone (DEX) and hydrocortisone. Hormone binding studies carried out in intact cell monolayers showed rapid uptake and binding of the [³H]DEX, which was independent of cell density at 37 C. The number of binding sites per cell decreased with increased age in vitro. Competition studies with several unlabeled steroids demonstrated high molecular specificity and a strong correlation between the ability of a steroid to compete for specific DEX binding sites and its ability to stimulate cell proliferation. Our observation that the number of specific glucocorticoid binding sites per cell decreased 40% without any significant change in affinity is similar to observations made in target tissues in aged animals. This finding may explain the previously reported decrease in responsiveness to these glucocorticoids in aging WI-38 cells.