Mineralocorticoid and glucocorticoid receptors at the neuronal membrane, regulators of nongenomic corticosteroid signalling

The balance between corticosteroid actions induced via activation of the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) determines the brain’s response to stress. While both receptors are best known for their delayed genomic role, it has become increasingly evident that they can also associate with the plasma membrane and act as mediators of rapid, nongenomic signalling. Nongenomic corticosteroid actions in the brain are required for the coordination of a rapid adaptive response to stress; membrane-associated MRs and GRs play a major role herein. However, many questions regarding the underlying mechanism are still unresolved. How do MR and GR translocate to the membrane and what are their downstream signalling partners? In this review we discuss these issues based on insights obtained from related receptors, most notably the estrogen receptor α.

► Nongenomic corticosteroid signalling in the brain coordinates rapid coping to stress.
► MR and GR reside in the membrane and mediate nongenomic corticosteroid signalling.
► Binding of MR and GR to caveolin-1 is required for rapid signalling.
► MR and GR activate components of common nongenomic steroid signalling pathways.