Developmental changes in the expression and compartmentalization of the glucocorticoid receptor in embryonic retina.

Abstract

Inducibility by glucocorticoids of the glutamine synthetase gene in chicken embryo retina and the transcriptional activity of the glucocorticoid receptor (GR) greatly increase between embryonic days 6 and 10 (E6, E10), although the level of GR does not markedly change during that time. This apparent discrepancy was investigated by exming the pattern of GR expression in undifferentiated E6 retina and in E10 retina, which consists mostly of differentiated cells. Two GR Isoforms, 90 and 95 kDa, were found to be expressed at both of these ages at a similar total level but in different proportions: in E6 retina the level of the 90-kDa isoform was higher, whereas in E10 retina the 95-kDa receptor was higher.However, following treatment of the retinas with cortisol, the 95-kDa isoform became the predominant receptor at both ages.Immunohistochemical analysis revealed that the cellular localization of GR markedly changed in the course of development: in the undifferentiated E6 retina GR was expressed in virtually all cells, whereas in the more differentiated E10 and E12 retina, GR was detected only in Mfiller glia cells. The latfer represent 20% of the cells in this tissue and are the only cells in which glucocorticoid hormone induces the glutamine synthetase gene.We suggest that the compatmentalization of GR in Muller glia is a majior aspect of the mechanism that modulates receptor activity during retina development and results in the temporal increase in the inducibility of glutamine synthetase and its specific localization in Mfuller glia cells.

Glutamine synthetase protects against neuronal degeneration in injured retinal tissue

“…Under normal conditions, amidation of glutamate to glutamine occurs in glial cells, which are the only cells in the retinal tissue that express GS (12,29,30). This could also be the case in injured tissue.…”

Cellular Processing of the Glucocorticoid Receptor Gene and Protein: New Mechanisms for Generating Tissue-specific Actions of Glucocorticoids

“…Whereas glucocorticoids induce the killing of lymphocytes, they have protective effects on cells of the endometrium, ovarian follicle, liver, and mammary epithelium (7). The sensitivity to glucocorticoids differs not only among individuals but also within tissues of the same individual and even within the same cell during the cell cycle (8,9).…”

A Silencer Element in the Regulatory Region of Glutamine Synthetase Controls Cell Type-specific Repression of Gene Induction by Glucocorticoids

“…Induction of gene expression requires a threshold level of active glucocorticoid receptor molecules; below that level, cells are not responsive to the hormone (41). This is the case in retinal neurons that do not express the receptor molecules, or express them only at low levels (1,16). In these cells GS is not inducible by glucocorticoids, despite the fact that NRSF is not expressed.…”

“…The direct involvement of glucocorticoids in the control of GS gene transcription is evidenced by the nuclear run-on transcription assay, as well as by the finding that the upstream region of the GS gene contains a glucocorticoid response element (GRE) that can bind the glucocorticoid receptor protein and confer responsiveness to glucocorticoids on an attached reporter gene (8 -10, 14, 15). This mode of regulation, which is dependent on the presence of active glucocorticoid receptor molecules, explains the cell type specificity of GS expression in the neural retina; GS expression is always restricted to Mü ller glial cells, which are the only cells in the tissue that express a detectable level of the glucocorticoid receptor protein (1,16). It does not, however, explain why various non-neural cells, which contain functional glucocorticoid receptor molecules capable of inducing other target genes, are not responsive to the hormone and express only low levels of GS.…”