Transcriptional regulation of steroid receptor coactivator-1 (SRC-1) in glucocorticoid action

Diverse mechanisms of steroid receptor action have been clarified in recent years, as a consequence of the discovery of multiple coactivators. Among t hem, steroid receptor coactivator-1 (SRC-1) is a member of the p160 coactiv ator families, which are 160 kDa proteins that interact with steroid recept ors in a hormone-sensitive manner. Since coactivators function as transcrip tional power boosters, subtle changes in coactivator expression levels in c ertain cells markedly change of receptor-mediated transcriptional activity. Expression of the glucocorticoid receptor (GR) has been shown to be autore gulated in glucocorticoid action, i.e., 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 coactivators, the SRC-1 mRNA level was downregulated by dexamethasone trea tment in rat tissues, such as liver, heart, kidney, stomach, and cerebrum, in vivo. We also demonstrated dexamethasone-cells in vitro. These results s uggest that ligand-mediated downregulation of SRC-1 is crucial in the physi ology of glucocorticoid action.