Fig. 1.

Glucocorticoids produce direct and indirect genomic actions as well as nongenomic signaling actions via glucocorticoid (GR) and mineralocorticoid (MR) receptors. These involve not only direct and indirect genomic actions, but also direct stimulation of glutamate release and stimulation of endocannabinoid production, which then feed back on glutamate and GABA release and actions in mitochondria to affect Ca⁺⁺ buffering and free radical formation (9, 10) (Upper Right). As shown in the article by Arango-Lievano et al. (2), BDNF, in the presence of glucocorticoids, phosphorylates the GR at sites that facilitate its translocation to the cell nucleus for transcriptional actions; this effect is synergistic with the ability of glucocorticoids to activate, via a genomic mechanism, the phosphorylation of the TrkB receptor independently of BDNF, thus creating a positive feedback loop.