Synthetic peptides derived from the steroid binding domain block modulator and molybdate action toward the rat glucocorticoid receptor.

Abstract

Modulators are endogenous low-mol-wt inhibitors of glucocorticoid receptor activation, and are mimicked by exogenous sodium molybdate. Activation involves the dissociation of the 90-kDa heat-shock protein from the receptor. The heat-shock protein is thought to bind to a conserved 20-amino-acid region in the steroid-binding domain of the receptor (595-614 of the rat protein). Synthetic peptides corresponding to this amino acid sequence prevented the modulators and sodium molybdate from inhibiting receptor activation. These results imply that the region 595-614 of the rat glucocorticoid receptor is also a modulator/molybdate binding site.