The interaction of estrogen- and antiestrogen-receptor complexes with polynucleotides.

As the polynucleotide domain of the estrogen receptor (Re) is a possible site for the modulation of Re activity, the interaction of antiestrogen (4-hydroxytamoxifen and tamoxifen)-receptor complexes (4-OH-Tam-Re and Tam-Re) with polynucleotides (oligodeoxynucleotide-cellulose, DNA-cellulose, and polyribonucleotide-agarose) was investigated and compared with that of the 17 beta-estradiol-receptor complex (E2-Re). E2-Re- and anti-Re-E2-complexes were optimally bound to oligo(dT)-cellulose and poly(U)-agarose at 0.15 M KCl and pH 7.6. Temperature activation of the Re was not required for these selective interactions to occur, but they were inhibited by 10 mM sodium molybdate. OH-Tam-Re and E2-Re demonstrated similar selectivity for different deoxynucleotide bases [oligo(dG) greater than oligo(dT) greater than or equal than oligo(dC) greater than oligo(dA) greater than or equal to oligo(dI)] and different ribonucleotide bases [poly(G) = poly(I) greater than poly(U) greater than poly(A) greater than or equal to poly(C)]. Quantitatively, Tam-Re bound significantly less to oligo(dT)-cellulose than did OH-Tam-Re, which did not differ significantly from E2-Re, a result probably related to the dissociation of the lower affinity ligand from the Re/oligo(dT)-cellulose during the assay procedure. Unoccupied Re also bound selectively to these synthetic polynucleotides. It is concluded that: 1) selective binding of Re to synthetic polynucleotides is inhibited by 10 mM sodium molybdate; 2) estradiol is not essential for selective binding to synthetic polynucleotides, since unoccupied Re was only slightly less efficiently bound than E2-Re; and 3) selective binding of Re to synthetic polynucleotides was unaffected by the agonist or antagonist properties of the ligand bound at the steroid-binding site. These data suggest that nonsteroidal antiestrogens are unlikely to exert their antagonist activity by modulating the function of the polynucleotide-binding site of Re.