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Control of transcription of responsive genes by steroid hormones is mediated by receptor proteins. Steroid receptors belong to a family of ligand dependent trans-acting regulatory proteins. The cellular glucocorticoid receptor concentration is modulated by a number of factors including glucocorticoids which down-regulates their own receptor concentration. Using human glucocorticoid receptor gene fused to bacterial chloramphenicol acetyltransferase and clonal human glucocorticoid receptor cDNA in an expression vector, we have directly demonstrated the receptor mediated down regulatory events. Furthermore, we have purified, from human MCF-7 cells a protein factor (GRF-1) that binds to the hGR gene promoter, cloned the cDNA corresponding to GRF-1 by a Agt-11 cDNA library and deduced the primary structure from the cDNA clone, produced GRF-1 in CV-1 and COS-1 cells using GRF-1 expression vector and studied the trans-repression of hGR gene in CV-1 and COS-1 cells. Studies on the effect of plasmids after co-transfection into CV-1 and COS-1 cells, showed that the cloned GRF-1 cDNA in Agt 11 was capable of receptor-dependent stimulation. We propose that stimulated expression of GRF-1 by glucocorticoids results in glucocorticoid-dependent trans-repression of the human glucocorticoid receptors.
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