Characterization of a steroid hormone receptor gene and mRNA in wild-type and mutant cells

The effects of steroid hormones are mediated by intracellular hormone-specific receptor proteins; the interaction between the hormone and its receptor increases the affinity of the receptor for nuclear binding sites, thereby modulating the expression of specific genes¹. The glucocorticoid receptor is a soluble protein of relative molecular mass (M _r) 94,000 (94K), present at a low relative abundance (≤0.01%); it has been purified to near-homogeneity^2,3, and specific antisera and monoclonal antibodies have been produced^4-6. Purified glucocorticoid receptor binds in vitro with high affinity to defined regions of DNA near regulated promoters^7-10, and sequences essential for these interactions are functional in vivo as hormone-dependent transcriptional enhancer elements^11,12. We have now cloned complementary DNA (cDNA) for the rat liver glucocorticoid receptor and we describe here a 2.6-kilobase (kb) receptor cDNA isolated following polysome immuno-enrichment of receptor messenger RNA with glucocorticoid receptor-specific antibodies. The receptor appears to be encoded by a single-copy gene which specifies a ∼6-kb transcript in rat and mouse cells; this mRNA is altered quantitatively and qualitatively in several mutant cell lines with specific defects in receptor function.