抄録
Adrenal corticosteroids readily enter the brain and exert markedly diverse effects, such as stress response of the target neural cells. These effects are regulated via two receptor systems, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR), both of which are ligand-dependent transcription factors. Moreover, various kinds of cofactors interact with these receptors for mediating their transcriptional effects. It has been shown that MR and GR are highly colocalized in the hippocampus that is a target of stress hormone and an especially plastic and vulnerable region of the brain. In this symposium, dynamics of MR and GR in living cultured hippocampal neurons and COS-1 cells will be presented using real time imaging technique with green fluorescent protein (GFP) including fluorescence recovery after photobleaching (FRAP). We will also present the subcelluar distribution of cofactors such as steroid receptor coactivator-1 (SRC-1). Effects of various kinds of substances on the nucleo-cytoplasmic trafficking of these receptors and cofactors, such as ligand, cytoskeletal elements, and carrier proteins of importin a and b, are investigated. Furthermore, we will discuss possible heterodimerization of MR and GR or interaction between corticosteroid receptor and SRC-1 in a single living cell by using fluorescence resonance energy transfer (FRET). Finally, we will show dynamics of GR in hippocampal neurons of GFP-GR knockin mouse. GFP-GR knockin mice may open new windows for analyzing GR functions from celluar to tissue level to yield innovative knowledge. [Jpn J Physiol 54 Suppl:S53 (2004)]
