Recombinant DNA Technologies in Neuroendocrinology

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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.