The glucocorticoid receptor in rat liver

Abstract

Glucocorticosteroids, in similarity to all other active steroid hormones, exert their biological effect uia a soluble receptor protein in the target cell. Twenty years ago Jensen and Jacobson first demonstrated the specific binding of [3H]-estradiol by rat uterus, a target organ for estrogens 111. Since then, a great deal of information has been obtained with regard to the mechanism of action of steroid hormones. A model for the mechanism of action of steroid hormones, in particdar gluco~o~icosteroids is shown in Fig. 1. There are separate proteins for androgens, estrogens, glucocorticosteroids, mineralocorticosteroids, gestagens and vitamin D, respectively. The steroid, in this case a glucocorticosteroid, passes through the cell membrane of the target cell, presumably by passive diffusion, into the cytoplasm. Here the steroid binds to specific receptor proteins and the complex is then translocated into the nucleus where it interacts with DNA. Before the nuclear translocation or interaction with DNA can take place in vitro, the GR* must be “activated”. “Activation” can be achieved by incubating the complex at 20” or by incubation at 0” in the presence of 0.12 M NaCl or RCI. Activation probably incurs a conformational change of the steroid receptor complex and presum-