ROLE OF THE C-TERMINUS OF THE GLUCOCORTICOID RECEPTOR IN HORMONE-BINDING AND AGONIST-ANTAGONIST DISCRIMINATION

The glucocorticoid receptor (GR) is a hormone-inducible intracellular modulator of specific gene transcription, Both glucocorticoids and pro gestins bind to the GR, and some progestins are able to activate the r eceptor, We have characterized a mutation of the mouse GR that restric ts transcriptional activation, but not hormone binding, to glucocortic oids, This mutation, Y770N, is located 13 amino acids from the C termi nus of the mouse GR and helps define a region of the receptor that is important for transcriptional specificity, To further characterize thi s region of the GR, we have constructed a series of chimeric receptors between the glucocorticoid, progesterone, and androgen receptors. We find that the C-terminal 14 amino acids of the GR can be replaced by t he equivalent region of the progesterone or androgen receptors with li ttle alteration in either hormone-binding specificity or transcription al response to agonists and antagonists, The region is required for ho rmone binding, however, since C-terminal deletions yield inactive rece ptors, We conclude that even though mutation of the C-terminal 14 amin o acids of the On can lead to alterations in hormone binding specifici ty and agonist potential, the differential hormone-binding capacities of the glucocorticoid, progesterone, and androgen receptors are not en coded in this region.