The glucocorticoid receptor and a putative repressor protein coordinately modulate glucocorticoid responsiveness of the mouse mammary tumor virus promoter in the rat hepatoma cell line M1.19.

Signal transduction by glucocorticoid hormones is mediated by the intracellular glucocorticoid receptor protein. The mechanisms determining cell type- or tissue-specific differences in hormone responsiveness remain, however, unclear. To address this issue we have used two different rat hepatoma cell lines, 762 and 6.10.2, respectively, in which mouse mammary tumor virus has been stably integrated. Nuclear extracts from both of these cell lines contained a factor that bound to a sequence motif extending from -163 to -147 in the mouse mammary tumor virus promoter and that appeared to repress hormonal induction of viral mRNA expression. Transient transfection experiments indicated that the cellular levels of this putative repressor did not affect basal promoter activity; this factor appeared rather to determine cellular sensitivity to glucocorticoids. Moreover, in these experiments the relative levels of the glucocorticoid receptor appeared to be the main determinant of maximum inducibility of virus expression by hormone. Taken together, these data indicate that the differential expression patterns of receptor versus the putative repressor protein may determine the level of hormonal responsiveness of target genes in glucocorticoid-sensitive tissues.