The second type of steroid-regulation is transrepression, the selective reduction in target gene expression. This activity is often mediated by monomer GR-ligand complexes interacting with transcriptional regulatory factors such as NF-κB, AP1 or STAT5.14 Transcriptional inhibition requires protein-protein interactions involving the GR transactivation domain, but there is typically no direct interaction between the GR and any nucleic acid response elements. A key to understanding current approaches in the development of newer, more selective GR agonists is the observation that anti-inflammatory effects of glucocorticoids are mediated primarily by transrepression