Identification of corticosteroid-responsive genes in rat hippocampus using serial analysis of gene expression.
Adrenal corticosteroids (CORT) have a profound effect on the function of the hippocampus. This is mediated in a coordinated manner by mineralocorticoid (MR) and glucocorticoid receptors (GR) via activation or repression of target 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 transduction 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 chosen CORT-responsive genes had distinct expression patterns in neurons of the 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 revealed that the majority of the CORT-responsive genes were regulated either by activated MR or by activated GR, while only a few genes were responsive to 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-responsive genes identified here will provide insight into the molecular mechanisms 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.
Datson
N A
NA
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Centre, 2300 RA Leiden, The Netherlands. datson_n@lacdr.leidenuniv.nl
van der Perk
J
J
de Kloet
E R
ER
Vreugdenhil
E
E
D000305:Adrenal Cortex Hormones / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D015723:Gene Library; D005796:Genes / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000235:genetics*; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D000305:Adrenal Cortex Hormones; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D012097:Repressor Proteins