Transcriptional control of glial fibrillary acidic protein and glutamine synthetase in vivo shows opposite responses to corticosterone in the hippocampus.

Transcriptional regulation of two astrocyte genes, glial fibrillary acidic protein (GFAP) and glutamine synthase (GS), by glucocorticoids was determined by nuclear run-on assay with hippocampal tissues from adult male F344 rats. Transcriptional responses of GFAP to corticosterone were slower than those observed for GS, but were more sensitive to changes in plasma corticosterone. The transcription of GFAP did not change 2 h after the injection of 10 mg corticosterone, but was reduced by 50% at 6 and 24 h. In contrast, corticosterone increased GS transcription at 2 and 6 h. Seven days after adrenalectomy, GFAP, but not GS, transcription was increased. Corticosterone replacement (200 micrograms/ml in the drinking water) suppressed GFAP, but did not increase GS transcription in adrenalectomized rats. Therefore, GFAP transcription is more sensitive to low physiological levels of corticosterone than transcription of GS. The slower response of GFAP than GS to corticosterone suggests that glucocorticoids may have indirect effects on GFAP expression that require additional transcriptional regulators besides the glucocorticoid receptor.