Antihormone-steroid hormonal activity, heat-shock protein hsp 90 and receptors

Antisteroid hormones compete for hormone binding at the receptor level and prevent the hormonal response. A new concept is proposed for explaining the antiglucocorticosteroid activity of RU 486 in the chick oviduct system. It is based on the ability of the antisteroid to stabilize the hetero-oligomeric 8S-form of the glucocorticosteroid receptor, which involves the interaction of the 94,000-dalton receptor and the heat-shock protein MW 90,000 (hsp 90). It is proposed that hsp 90 caps the DNA-binding site of the receptor, and this prevents it from binding to the DNA of hormone regulatory elements and to increase transcription of regulated genes. This paper reviews other antiglucocorticosteroid and antiestrogen systems with reference to this hypothesis, and also describes a four-step analysis of the molecular mechanism of antisteroid hormone action at the receptor level.