Identification of corticosteroid-responsive genes in rat hippocampus usingserial analysis of gene expression

Adrenal corticosteroids (CORT) have a profound effect on the function of th e hippocampus. This is mediated in a coordinated manner by mineralocorticoi d (MR) and glucocorticoid receptors (GR) via activation or repression of ta rget genes. The aim of this study was to identify, using serial analysis of gene expression (SAGE), CORT-responsive hippocampal genes regulated via MR and/or GR. SAGE profiles were compared under different conditions of CORT exposure, resulting in the identification of 203 CORT-responsive genes that are involved in many different cellular processes like, energy expenditure and cellular metabolism; protein synthesis and turnover; signal transducti on and neuronal connectivity and neurotransmission. Besides some previously identified CORT-responsive genes, the majority of the genes identified in this study were novel. In situ hybridization revealed that six randomly cho sen CORT-responsive genes had distinct expression patterns in neurons of th e hippocampus. In addition, using in situ hybridization, we confirmed that these six genes were indeed regulated by CORT, underscoring the validity of the SAGE data. Comparison of MR- and GR-dependent expression profiles reve aled that the majority of the CORT-responsive genes were regulated either b y activated MR or by activated GR, while only a few genes were responsive t o both activated MR and GR. This indicates that the molecular basis for the differential effects of activated MR and GR is activation or repression of distinct, yet partially overlapping sets of genes. The putative CORT-respo nsive genes identified here will provide insight into the molecular mechani sms underlying the differential and sometimes opposing effects of MR and GR on neuronal excitability, memory formation and behaviour as well as their role in neuronal protection and damage.