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 patterns of gene expression. A glial-specific pattern, for example, is shown by the glucocorticoid-inducible gene glutamine synthetase. The enzyme is expressed at a particularly high level in glial cells, where it catalyzes the recycling 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 elements, a glucocorticoid response element and a neural restrictive silencer element. Though not glial specific by themselves, these elements may establish a glial-specific pattern of expression through their mutual activity and their combined effect. The inductive activity of glucocorticoids is markedly repressed by the c-Jun protein, which is expressed at relatively high levels in proliferating glial cells. The signaling pathway of c-Jun is activated 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 receptor and thus represses glutamine synthetase expression. This repressive mechanism might also affect the ability of glial cells to cope with glutamate neurotoxicity in injured tissues. Copyright 1999 John Wiley & Sons, Inc.