Glucocorticoid control of glial gene expression

The glucocorticoid signaling pathway is responsive to a considerable number of internal and external signals and can therefore establish diverse patte rns of gene expression. A glial-specific pattern, for example, is shown by the glucocorticoid-inducible gene glutamine synthetase. The enzyme is expre ssed at a particularly high level in glial cells, where it catalyzes the re cycling of the neurotransmitter glutamate, and at a low level in most other cells, for housekeeping duties. Glial specificity of glutamine synthetase induction is achieved by the use of positive and negative regulatory elemen ts, a glucocorticoid response element and a neural restrictive silencer ele ment. Though not glial specific by themselves, these elements may establish a glial-specific pattern of expression through their mutual activity and t heir combined effect. The inductive activity of glucocorticoids is markedly repressed by the c-Jun protein, which is expressed at relatively high leve ls in proliferating glial cells. The signaling pathway of c-Jun is activate d by the disruption of glia-neuron cell contacts, by transformation with v- src, and in proliferating retinal cells of early embryonic ages. The c-Jun protein inhibits the transcriptional activity of the glucocorticoid recepto r and thus represses glutamine synthetase expression, This repressive mecha nism might also affect the ability of glial cells to cope with glutamate ne urotoxicity in injured tissues. (C) 1999 John Wiley & Sons, Inc.