Synopses & Reviews
This volume covers new aspects and future directions in molecular neuroendocrinology, an important and rapidly growing area in neuroendocrinology. Among the various neurotransmitters or neuromodulators that play an important role in the control of endocrine functions, neuropeptides and related proteins have drawn special attention because of their diversity and complexity in action. More recently, molecular biology has become an essential tool of research in this area. Various genes encoding neuropeptides and other related pro- teins have been cloned, and the regulation of expression of these genes has been studied extensively. Transgenic animals have been used in studying the function of the gene in que- stion. In-situ hybridization is being applied to localize the site of production and analyze the regulation of pro- duction of peptides or proteins.
Synopsis
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.