RU486 (an anti-steroid hormone) receptor structure and heat shock protein mol. wt 90,000 (hsp 90).

Anti-steroid hormones compete for hormone binding at the receptor level and prevent the hormonal response. A new parameter is proposed for explaining both anti-progesterone and anti-glucocorticosteroid activities of RU486, a synthetic derivative of high receptor affinity. It is based on its ability to stabilize the heterooligomeric 8S form of the glucocorticosteroid (in the chick oviduct system) and progesterone (in the rabbit uterus system) receptors. These 8S complexes involve the interaction of the approximately 94,000 and approximately 120,000 mol. wt receptors with the heat shock protein of the mol. wt approximately 90,000 (hsp 90). It is proposed that hsp 90 caps the DNA binding site of the receptor and that this would prevent it from binding to the DNA of hormone regulatory elements (HRE) and modifying transcription of regulated genes. In contrast, hormone agonists induce the dissociation of the oligomer, thus unmasking the functional DNA binding domain of the receptor. Whether other differences between agonist- and antagonist-receptor complexes are involved in the expression of hormone and anti-hormone effects also is discussed in this paper.