Why do we need nongenomic glucocorticoid mechanisms?

• We review the literature on nongenomic actions of GCs related to stress.
• We propose reasons why nongenomic mechanisms of GC actions are needed.
• We propose the physiological significance of the inherent nongenomic GC actions.

Glucocorticoids (GCs) are a class of steroid hormones that have been known to be involved in various physiological processes and to play a pivotal role in preserving basal and stress-related homeostasis. GCs are also widely used clinically as anti-inflammatory, immunosuppressive, anti-shock drugs. It is believed traditionally that GCs exert most of their effects genomically. In addition to the well-known classical genomic mechanisms, GCs also affect various functions via rapid, nongenomic mechanisms. The therapeutic benefits of nongenomic GC actions have been exploited in clinical medicine, especially with high-dose pulsed glucocorticoid administration. However, it is certainly not the case that the inherent nongenomic glucocorticoid mechanisms evolved only for their clinical utility. Here, we review the recent literature on nongenomic actions of GCs related to stress and the physiological significance of these actions, and we propose reasons why nongenomic mechanisms of GC actions are needed.