Unraveling the functions of the membrane-bound glucocorticoid receptors: first clues on origin and functional activity

Glucocorticoids (GCs) are routinely used to treat a wide range of rheumatic and other inflammatory diseases. GCs are steroidal drugs that exert their strong anti-inflammatory and immunosuppressive effects via genomic mechanisms, primarily by signaling through the cytosolic glucocorticoid receptor. In addition, rapid, nongenomic responses following GC treatment have been reported to involve signaling via the membrane-bound glucocorticoid receptor (mGR). Since an important clinical role of this receptor has been proposed, investigations regarding the origin and function of the mGR are currently performed in order to understand rapid GC signaling and to optimize treatment strategies with GCs. Here, we summarize the current knowledge on the mGR and compare these findings to results obtained for other membrane-bound receptors, such as membrane forms of the estrogen and progesterone receptors.