Nontranscriptional actions of the glucocorticoid receptor.
Many cellular responses to corticosteroids involve the transcriptional modulation of target genes by a prototypical nuclear receptor, the glucocorticoid receptor (GR). In the classic model of steroid hormone action 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 nontranscriptional effects of GR in the vascular system. The nontranscriptional 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. This novel pathway of steroid hormone action protects against ischemic injury by augmenting blood flow and decreasing vascular inflammation.
Limbourg
Florian P
FP
Vascular Medicine Research, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA.
Liao
James K
JK
D000305:Adrenal Cortex Hormones / Q000378:metabolism / Q000627:therapeutic use; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D000305:Adrenal Cortex Hormones; D004247:DNA; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011965:Receptors, Glucocorticoid; C496314:NOS3 protein, human; C494918:AKT1 protein, human