Nuclear interactions of zearalanol-oestrogen receptor complexes in rat liver: a comparison with oestradiol-17 beta.

Nuclear interactions of alpha-zearalanol (P-1496) and oestradiol-17 beta (E2) were compared following binding of these compounds to cytosolic oestrogen receptor. A single dose of P-1496 (400 micrograms) or E2 (25 micrograms) given subcutaneously to ovariectomized female rats resulted in two peaks of nuclear oestrogen-receptor concentrations at approx. 0.5 and 4.5 h and showed no qualitative differences between the two compounds. Under in vitro cell-free conditions, [3H]P-1496 was also able to cause oestrogen receptor retention by liver nuclei. Moreover, analysis of salt-extracted nuclear-bound receptor on sucrose gradients gave similar results to those obtained using [3H]E2 with a main peak of radioactivity sedimenting at 5S. Using [3H]P-1496, the time-course of nuclear retention was examined in both males and females. These studies showed no sex difference with nuclear-bound radioactivity reaching a plateau between 20-30 min. The ability of oestrogen-receptor complexes to bind to DNA was examined by DNA-cellulose chromatography. Using either [3H]E2 or [3H]P-1496 as the ligand, qualitative sex differences were shown in the number of peaks present. A comparison of chromatographic patterns obtained with the two ligands suggested close similarities in non-covalent DNA binding between the two compounds, in both males and females. These studies indicate that P-1496 is capable of causing retention of oestrogen receptor by liver nuclei and it binds to DNA in a manner similar to E2. Hence, our data do not explain the marked difference in oestrogenic activity observed in vivo between E2 and P-1496.