The inhibition of prolactin synthesis in GH₃ rat pituitary tumor cells by monohydroxytamoxifen is associated with changes in the properties of the estrogen receptor

E₂ (1 nM) stimulated the synthesis of PRL in GH₃ cells. OH TAM (100 nM) did not affect basal PRL synthesis, but completely inhibited the increase produced by 1 nM E₂. [³H]E₂ and [³H]OH TAM both bound to the cytosolic 8S ER and these were split into 4S subunits on sucrose gradients containing 0.4 M KCl. By comparison, ER complexes extracted from nuclei of GH₃ cells cultured in media containing [³H]E₂ or [³H]OH TAM both sedimented at 5S on sucrose gradients containing 0.4 M KCl. Both 4S and 5S ER complexes were recognized by the monoclonal antibody D547 which increased their sedimentation coefficients to 8-9S. In contrast, a polyclonal antibody raised to calf uterine ER in the goat, interacted with the cytosolic ER so that the binding of [³H]E₂ was inhibited but the binding of [³]OH TAM was only slightly reduced. A molecular model is proposed to describe the binding of E₂ and OH TAM to the ER that might contribute to an understanding of estrogen and antiestrogen action.