Glucocorticoid receptor homodimers and glucocorticoid-mineralcorticoid receptor heterodimers form in the cytoplasm through alternative dimerization interfaces

Steroid hormone receptors act to regulate specific gene transcription prima rily as steroid-specific dimers bound to palindromic DNA response elements. DNA-dependent dimerization contacts mediated between the receptor DNA bind ing domains stabilize DNA binding. Additionally, some steroid receptors dim erize prior to their arrival on DNA through interactions mediated through t he receptor ligand binding domain. In this report, we describe the steroid- induced homomeric interaction of the rat glucocorticoid receptor (GR) in so lution in vivo. Our results demonstrate that GR interacts in solution at le ast as a dimer, and we have delimited this interaction to a novel interface within the hinge region of GR that appears to be both necessary and suffic ient for direct binding. Strikingly, we also demonstrate an interaction bet ween GR and the mineralocorticoid receptor in solution in vivo that is depe ndent on the ligand binding domain of GR alone and is separable from homodi merization of the glucocorticoid receptor. These results indicate that func tional interactions between the glucocorticoid and mineralocorticoid recept ors in activating specific gene transcription are probably more complex tha n has been previously appreciated.