Recombinant DNA Technologies in Neuroendocrinology

1.1 Mechanism of Action of Glucocorticoid Hormones The current model of glucocorticoid hormone action is summarized in Fig. 1. After synthesis, glucocorticoids are secreted into the blood stream and trans- ported to target cells where they bind with high affinity (K-1O-9M) and d specificity to the intracellular glucocorticoid receptor (GR) protein. The sub- cellular localization of hormone-free GR is still a controversial issue. However, most data support the idea that unliganded GR is in the cytoplasmic compartment or loosely associated with the nucleus (Picard and Yamamoto 1987; Gustafsson et al. 1987 and references therein; LaFond et al. 1988; Gasc et al. 1989). Upon ligand binding, GR is activated into a form capable of interacting with DNA. The mechanism of GR activation probably involves a conformational change and dis- sociation from nonreceptor components, e.g., the 90-kDA heat shock protein (hsp90: Pratt et al. 1988; Bresnick et al. 1989; Denis and Gustafsson 1989). The subcellular location of activated GR has been firmly established to be inside the nucleus. In vivo, the hormone-receptor complex interacts with specific DNA Activation r:::.. ~ qc [!3-GC ...&.GC~ j ~ ? , BIOLOGICAL EFFECTS " t , Active Protein , , ~Vl\lent.