Glucocorticoids (GCs) influence a great variety of cellular functions by at 
least three important modes of action: the activation (or repression) of genes 
controlled by binding sites for the glucocorticoid receptor (GR), the induction 
of apoptosis in lymphocytes and the recently discovered cross-talk to other 
transcription factors such as NF-kappaB. In this study we systematically 
compared various natural and synthetic steroid hormones frequently used as 
therapeutic agents on their ability to mediate these three modes of action. 
Betamethasone, triamcinolone, dexamethasone and clobetasol turned out to be the 
best inducers of gene expression and apoptosis. All GCs including the 
antagonistic compound RU486 efficiently reduced NF-kappaB-mediated 
transactivation to comparable extents, suggesting that ligand-induced nuclear 
localization of the GR is sufficient for transrepression. Glucocorticoid 
treatment of cells did not result in elevated IkappaB-alpha expression, but 
impaired the tumor necrosis factor (TNF)-alpha-induced degradation of 
IkappaB-alpha without affecting DNA binding of NF-kappaB. The structural 
requirements for the various functions of glucocorticoids are discussed.