The enzyme glutamine synthetase (GS) ranks as one of the most remarkable glucocorticoid-inducible vertebrate genes. However, little is known about the responsible DNA elements and the mode of glucocorticoid action. This is especially the case for the induction of GS in hepatoma cells. In the work presented, the rat hepatoma cell line FAO was used as a model to study the induction of GS under the influence of glucocorticoids. FAO, cells do not show GS activity in the absence of glucocorticoids and are strongly responding to their presence. Analyzing sequences of several thousand base pairs upstream and downstream from the transcriptional start point of the GS gene, a glucocorticoid responsible element was identified within the first intron of the gene. However, evidence is presented that aside from a primary effect on transcription glucocorticoids mediate their effect on the expression of GS also at the posttranscriptional level. (C) 2002 Elsevier Science (USA). All rights reserved.