| dc.description.abstract | Glucocorticoids (GC) are frequently used as important drugs in clinical practice of pediatrics. As well as, they have important physiologic functions; they have immune suppressive, antiinflammatory and anti-allergic effects that they exert on primary and secondary immune cells, tissues and organs. Their therapeutic effects are considered to be mediated by four different mechanisms of action: the classical genomic mechanism of action caused by the cytosolic glucocorticoid receptor (cGR); secondary non-genomic effects which are also initiated by the cGR; membrane-bound glucocorticoid receptor (mGR)-mediated nongenomic effects and finally non-specific, non-genomic effects caused by interactions with cellular membranes. Mechanisms of GR action are transactivation (GR binds to a related element in the promoter region of GC sensitive genes, inducing gene transcription) and transrepression (GR binds to a negative related element in a promoter region of GC-regulated genes that inhibit gene transcription by interfering with the binding of activating transcription factors). The underlying molecular mechanisms for their side effects are complex and frequently partly understood. Recent data suggest that certain side effects are predominantly mediated via transactivation (e.g., diabetes, glaucoma), whereas others are mediated via transrepression (e.g., suppression of the hypothalamic-pituitary-adrenal axis). In this review, we aimed to look at new molecular mechanisms of effects and side effects in relationship with apoptosis and caveolin, intracellular transport and endoplasmic reticulum stress, resistance mechanisms and new drugs developed based on these topics of GCs. © 2009 OMU All rights reserved. | en_US |
