AB - Diverse mechanisms of steroid receptor action have been clarified in recent years, as a consequence of the discovery of multiple coactivators. Among them, steroid receptor coactivator-1 (SRC-1) is a member of the p160 coactivator families, which are 160 kDa proteins that interact with steroid receptors in a hormone-sensitive manner. Since coactivators function as transcriptional power boosters, subtle changes in coactivator expression levels in certain cells markedly change of receptor-mediated transcriptional activity. Expression of the glucocorticoid receptor (GR) has been shown to be autoregulated in glucocorticoid action, ., GR is downregulated by its cognate ligand, indicating that this autoregulation of GR may protect target cells against excessive hormone action. In the present study, we examined whether coactivator expression levels are also regulated by glucocorticoids. Among several coactivators, the SRC-1 mRNA level was downregulated by dexamethasone treatment in rat tissues, such as liver, heart, kidney, stomach, and cerebrum, in vivo. We also demonstrated dexamethasone-mediated downregulation of SRC-1 mRNA and its protein levels in rat renal mesangial cells in vitro. These results suggest that ligand-mediated downregulation of SRC-1 is crucial in the physiology of glucocorticoid action.
The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA . These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The mediator of RNA polymerase II transcription subunit 1 protein is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID , is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes [., thyroid hormone receptor -(TR-) associated proteins that interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors]. It also regulates p53 -dependent apoptosis and it is essential for adipogenesis . This protein is known to have the ability to self-oligomerize.