This study is directed towards examining the onset and control, during development, of glucocortocoid receptor inducible regulatory systems. We plan to examine the developmental generation of this system using early mouse stem cell systems and also the mouse embryo. Our starting point is the mouse embryonal carcinoma cell (or EC cell) since we and others have shown the absence of a glucocortocoid system in these stem cells. We plan to examine the basis(es) for the absence of a glucocortocoid response in mouse embryonal carcinoma cells through examination of glucocortocoid receptor levels, the expression and nature of glucocortocoid receptor mRNA levels, and through introducing vectors for expression of the glucocortocoid receptor. Using stem cell lines and mouse embryos, we plan to examine the developmental timing of the onset of the glucocortocoid response, its possible role in early differentiation and whether we might interfere with this role through gene transfer experiments.
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