THE BINDING OF [³H]‐OESTRADIOL‐17β IN THE IMMATURE RAT UTERUS DURING THE SEQUENTIAL ADMINISTRATION OF NONSTEROIDAL ANTI‐OESTROGENS

The binding of [³H]‐oestradiol‐17β (0.08 μg) in the uterus, vagina, liver and heart of immature female rats has been studied in vivo and the effect of daily administrations of the non‐steroidal anti‐oestrogens, tamoxifen and monohydroxytamoxifen, on the 2h accumulation of [³H]‐oestra‐diol‐17β in the uterus has been determined. Doses of tamoxifen (8 μg daily) or monohydroxytamoxifen (1.28 μg daily), which have previously been found to antagonize completely the uterotrophic activity of oestradiol‐17β (0.08 μg daily), did not significantly reduce the total uterine binding of 0.08 μg [³H]‐oestradiol‐17β administered on day 4 of a 3‐day uterine weight test. The simultaneous administration of tamoxifen (8 μg) or monohydroxytamoxifen (1.28 μg) with [³H]‐oestradiol‐17β (0.08 μg) on day 3 of a uterine weight test did not significantly reduce the total uterine binding of oestradiol‐17β. The binding of [³H]‐oestradiol‐17β was reduced if monohydroxytamoxifen or tamoxifen was administered 4 h before the oestradiol. Tamoxifen (8 μg daily) or monohydroxytamoxifen (1.28 μg daily) did not prevent the translocation of [³H]‐oestradiol (0.08 μg) to the uterine cell nucleus on day 3 of a 3‐day uterine weight test. The measurement of total nuclear oestrogen receptors by an exchange assay technique demonstrated a higher concentration of oestrogen receptors in anti‐oestrogen‐treated animals compared with controls. Since the administration of anti‐oestrogenic doses of non‐steroidal anti‐oestrogens during a 3‐day uterine weight test did not inhibit the total binding of oestradiol in the uterus, or affect the translocation of the steroid to the nucleus, the mechanism of action of non‐steroidal anti‐oestrogens over the range of the partial agonist dose‐response curve must involve an interaction, or competition of oestradiol‐17β‐ and anti‐oestrogen‐oestrogen receptor complexes for sites within the nucleus. 1979 British Pharmacological Society