BIOLOGICAL RESPONSES OF ICI-164,384 AND OTHER ANTIESTROGENS IN VAGINAL AND UTERINE CELLS OF FETAL GUINEA-PIG IN CULTURE

The biological response of the anti-estrogens, ICI 164,384, 4-hydroxytamoxifen and tamoxifen were studied in isolated cells of the vagina and uterus of fetal guinea pig in culture. ICI 164,384 in these two cell lines provokes a significant stimulatory effect on the progesterone receptor levels. This is in opposition to available information where this compound is considered to have full anti-estrogenic properties. At the concentration of 10(-8) mol/l ICI 164,384 stimulates progesterone receptor 2-3 times in relation to the non-treated cells. 4-hydroxytamoxifen acts as an agonist in the vaginal cells, but as an antagonist in the uterine cells, in which it can block the stimulatory effect provoked by ICI 164,384. Progesterone, which inhibits progesterone receptor, can block in both cells the stimulatory action of ICI 164,384. No effect of the different compounds tested was found in proliferation or [H-3]thymidine incorporation. The agonistic effect of the anti-estrogen ICI 164,384 adds new information about the complexity of the mechanism of anti-estrogen action and gives additional models to explore the biological responses of these compounds.