The dynamic pattern of glucocorticoid receptor-mediated transcriptional responses in neuronal PC12 cells.

摘要

The aim of the current study was (i) to examine the overlap in the pattern of glucocorticoid receptor (GR)-mediated transcriptional responses between different neuronal substrates and (ii) to assess the nature of these responses by differentiating between primary and downstream GR-responsive genes. For this purpose, nerve growth factor-differentiated catecholaminergic PC12 cells were used in which endogenous GRs were activated briefly with a high dose of corticosterone followed by gene expression profiling 1 and 3 h afterwards using Affymetrix GeneChips. The results revealed a strikingly similar temporal pattern to that which was reported previously in hippocampus, with only down-regulated genes 1 h after GR activation and the majority of genes up-regulated 3 h after GR activation. Real-time quantatitive PCR of transcripts in cycloheximide-treated cells showed that all five GR-responsive genes selected from the 1-h time point were primary responsive, whereas all four GR-responsive genes selected from the 3-h time point were downstream responsive. At the level of individual genes, the overlap with the previously generated hippocampal data sets was small, illustrating the cell-type specifity of GR-mediated genomic responses. Finally, we identified a number of interesting genes, such as SWI/SNF, synaptosomal-associated protein 25 and certain Rab proteins which may play a role in the effects of glucocorticoids on catecholaminergic neuronal functioning.