Studies of the Mechanism of Glucocorticoid Hormone Action

Within the past two decades, much information has been gained about the action of glucocorticoid hormones. These steroids penetrate the cell membrane (by mechanisms as yet unknown) and bind to soluble cellular receptors. There then occurs a conformational change (or changes) of the gluco-corticoid-receptor complex (termed activation) such that the complex binds to the nuclear chromatin. After this association with chromatin, there are, in some cases, changes in the chromatin structure and, in most cases, effects on the levels of specific mRNA’s. Regarding the details of these steps, however, a number of questions remain to be answered. For instance, it has not been at all clear whether the receptor is a single polypeptide chain or whether it contains several subunits. The nature of the glucocorticoid-receptor interaction is not understood in detail, and little is known about the mechanism(s) by which the mRNA increases occur. In this report we present our investigation of a number of these steps in glucocorticoid hormone action through studies with cultured rat hepatoma and pituitary tumor cells.