Selected targets of GCR-alpha
Selected targets of GCR-alpha Glucocorticoid receptors are nuclear hormone receptors that belong to the superfamilyof ligand-activated transcription factors. Nuclear receptor subfamily 3 group C member 1( GCR-alpha ) is the major isoform of glucocorticoid receptors expressed in manytissues. Like other members of the family, the GCR-alpha possesses a modularstructure consisting of three major domains: N-terminal (NTD), DNA binding (DBD), andligand binding (LBD). Glucocorticoid molecules bind equimolarly toGCR-alpha and cause dimerization and translocation of the protein to the nucleus,where it bind to glucocorticoid response elements (GRE) on glucocorticoid-responsivegenes, resulting in increased transcription of target genes . Glucocorticoids are widely used for the suppression of inflammation in chronicinflammatory diseases such as asthma, rheumatoid arthritis, inflammatory bowel diseaseand autoimmune diseases , . This effect may be realizedvia GCR-alpha -dependent transcriptional regulation of immunological andinflammatory signaling proteins, such as Interleukin 4 ( IL-4 ) ,Interleukin 8 ( IL-8 ) , Interleukin 6 ( IL-6 ) , Toll-like receptor 2 ( TLR2 )  and others. Natural Glucocorticoids are essential components of the body neuroendocrinesystem, modulating the physiological homeostasis and coordinating the adaptive responsesto stressors. Whereas physiological levels of Glucocorticoids are required forproper metabolic control, excessive Glucocorticoids action has been tied to avariety of pandemic metabolic diseases, such as type II diabetes and obesity , , . GCR-alpha regulates transcriptionof Insulin , Insulin receptor , Insulin-likegrowth factor binding protein 1 ( IBP1 ) , Leptin , LIPIN1 . GCR-alpha is essential for regulation of developmental signaling. It playsimportant role in synaptic maturation , gametogenesis and pathological processes such as osteoporosis , ,muscular dystrophy  and others. These effects may be realized viaGCR-alpha -dependent regulation transcription of developmental and cytoskeletalsignaling proteins, such as Follicle stimulating hormone beta polypeptide (FSH-beta ) , Tumor necrosis factor (ligand) superfamily member 11( RANKL(TNFSF11) ) , and Elastin . In addition, GCR-alpha plays important role in toxicological processesstimulating transcription of xenobiotic-sensing receptors Nuclear receptor subfamily 1group I members 2 and 3 ( PXR and CAR )  and someCytochromes P450 , .