Transcriptional regulation of glial fibrillary acidic protein by corticosterone in rat astrocytes in vitro is influenced by the duration of time in culture and by astrocyte-neuron interactions

In the rat hippocampus and cortex, the transcription of glial fibrillary acidic protein (GFAP), an astrocyte intermediate filament protein, is inhibited by glucocorticoids. The present study examined the regulation of GFAP expression by glucocorticoids in astrocytes in vitro. Corticosterone (CORT) increased GFAP messenger RNA, protein, and transcription rates in cultured primary neonatal astrocytes, responses opposite the GFAP responses to CORT in vivo. The direction of GFAP regulation by corticosterone in vitro is reversed by coculture with neurons or by extended culture for 3 months. The switch in the direction of GFAP regulation by CORT during prolonged culture is associated with a 3-fold increased prevalence of type II glucocorticoid receptor (GR). These findings were corroborated with a promoter construct that contained 1.9 kilobases of 5'-up-stream rat GFAP DNA with a luciferase reporter. Thus, the direction of GFAP transcription to CORT is subject to the postreplicative time in culture and to interactions with neurons, in which 5'-up-stream sequences contain sufficient information to mediate the switch in the direction of the response to CORT. This in vitro model may be used to analyze how interactions of astrocytes with neurons or other cell types influence the hormonal regulation of GFAP.