CELL-TO-CELL CONTACTS CONTROL THE TRANSCRIPTION ACTIVITY OF THE GLUCOCORTICOID RECEPTOR

Contact interactions between glia and neurons are required for hormonal induction of glutamine synthetase in Muller glial cells. Glucocorticoids induce a pronounced increase in glutamine synthetase gene transcription in the intact retinal tissue but not in separated retinal cells. However, if the separated cells are reaggregated and glial cells reestablish contacts with neurons, glutamine synthetase inducibility is restored. This study examines the possible involvement of the glucocorticoid receptor (GR) in cell contact control of glutamine synthetase induction. Using the glucocorticoid-inducible reporter construct, p Delta G46TCO, and control constructs that are not inducible by glucocorticoids, we demonstrated that the trans-activating capability of GR markedly declines upon cell separation. Analysis of GR protein revealed that cell separation results in a pronounced decrease in GR expression. This decrease temporally correlated with the decline in glutamine synthetase gene transcription. Cell separation also results in a marked increase in c-Jun expression. This increase might be related to the decline in GR activity since elevation of c-Jun expression in the intact tissue inhibits the transcription activity of GR. Overexpression of GR by transfection of a GR expression vector or activation of endogenous GR molecules by 8-bromo-cAMP enhanced the responsiveness of separated retinal cells to glucocorticoids. These results demonstrate that transcription activity of the receptor protein depends on contact interactions between retinal cells and suggest that GR is involved in cell contact control of glutamine synthetase induction.