Glucocorticoid Binding Proteins in Human Leukaemic Lymphoblasts

Abstract

The binding of steroid hormones to highly specific cytoplasmic receptor proteins has been shown to be the first step in steroid hormone action in many systems¹. These steroid binding proteins (SBP) seem to be found exclusively in target tissues, and their kinetics of association and dissociation as well as their affinity for steroids correlate very well with biologic effects of the hormone^2–6. SBP can be readily demonstrated in cells such as rat thymocytes and mouse lymphosarcoma cells in culture, and these cells are lysed by glucocorticoids^7,8. Conversely, when steroid resistant cell lines are cloned from mouse lymphoma cells, a marked decrease in SBP has been demonstrated⁹. In addition, loss of the biologic effect of glucocorticoids has been correlated with a decrease in SBP in cultured hepatoma and fibroblast cells^10,11. As yet it has not been determined whether glucocorticoid receptors are of similar importance in human disease, and so we examined human leukaemic lymphoblasts to see if a specific SBP was detectable, and whether or not its presence or absence would correlate with glucocorticoid response in clinical situations and intact cells in culture. Very significant morbidity and mortality are associated with glucocorticoid therapy, particularly in the treatment of human malignancy^12,13. The eventual goal would be the development of a rapid and reliable in vitro test to predict steroid responsiveness in human leukaemic cells and thus avoid the hazards of unnecessary steroid therapy.