Glucocorticoids gene activation

Wallberg, A.E., Neely, K.E., Hassan, A.H., Gustafsson, J.A., Workman, J.L., and Wright, A.P. (2000) Recruitment of the SWI-SNF chromatin remodeling complex as a mechanism of gene activation by the glucocorticoid receptor taul activation domain. Mol. Cell. Biol. 20, 2004-2013. 

All of these hormones produce their effects after a characteristic lag period of 30 minutes to several hours—the time required for the synthesis of new proteins. This means that the gene-active hormones cannot be expected to alter a pathologic state within minutes (eg, glucocorticoids will not immediately relieve the symptoms of acute bronchial asthma). 

Table 2 Nuclear receptors (NR) for enzyme inducers. Enzyme inducers are now known to act as ligands to nuclear receptors, leading to gene activation and increased synthesis of the enzyme. Affinity of inducers to die receptors is now known to be responsible for the differential induction potential and can explain die observed species-differences in induction. The receptors tabulated are aryl hydrocarbon receptors (AhR), constituitively androstane receptor (CAR), pregnane X receptor (PXR), and glucocorticoid receptor (GR). The isoforms in bold type are the major isoform regulated by the corresponding receptors.

The cDNAs for the glucocorticoid and the oestrogen receptors were isolated more than 15 years ago. They were among the first genes, coding for transcriptional gene activators, to be identified. The family of nuclear receptors is the largest family of transcription factors. Until now, more than 150 different members of the superfamily of nuclear receptors, from worms to insects to humans, have been described. The discovery of an insect receptor for a steroid hormone, ecdysone, indicated that this kind of receptor must have evolved prior to the separation of vertebrates and invertebrates. 

GRE. (glucocorticoid response element). The glucocorticoid receptor is essentially a transA binding site in a promoter to which the activated glucocorticoid receptor can bind to a transcription factor which is activated only in the presence of glucocorticoids. The activated receptor will bind to a GRE, and transcription of the adjacent gene will be altered. See response element. 

The steroids are examples of gene-active hormones. The steroid diffuses into the cells (lower figure. ) where it binds to cytoplasmic glucocorticoid receptors S). In the absence of cortisol, the receptor is... 

Patejunas, G. Young, AP. (1990). Constitutive and glucocorticoid-mediated activation of glutamine synthetase gene expression in developing chicken retina. J. Biol. Chan., 265, 15280-5. 

Transactivation. Protein synthesis is initiated or inhibited by the action of the activated GR on DNA. The use of glucocorticoids leads to antiinflammatory effects by first controlling gene expression, which subsequentiy leads to the synthesis and/or suppression of inflammation regulatory proteins. 

The importance of cross-talk in GR actions is indicated by the construction of a GR dimerisation-deficient mutant mouse in which GR is unable to dimerise and therefore bind to DNA, thus separating the DNA-binding (transactivation) and inflammatory gene repression (transrepression) activities of glucocorticoids. In these animals dexamethasone was able to inhibit AP-1- and NF-kB-mediated gene transcription,... 

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