Non-genomic activation of protein kinase Akt by steroid hormones

Many cellular responses to steroid hormones involve the transcriptional modulation of target genes by the prototypical nuclear hormone receptor. In the classic model of steroid hormone action, the glucocorticoid receptor (GR) acts as ligand-dependent transcription factor by either activating or repressing gene expression through direct interactions with DNA or other transcription factors. Recent evidence suggests an important role for non-transcriptional effects of GR in the vascular system. The non-transcriptional actions of GR involve the rapid activation of protein kinases, such as phosphatidylinositol-3 kinase and Akt, leading to the activation of endothelial nitric oxide synthase (eNOS). This novel pathway of steroid hormone action protects against ischemic injury augmenting blood flow and decreasing vascular inflammation.