THE USE OF IN VIVO VAGINAL TTC REDUCTION OF SPAYED MICE FOR THE STUDY OF MODE OF ACTION OF ANTI-ESTROGENS

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The study was made on the relationship between in vivo vaginal TTC reduction and the epithelial histology of mouse vagina under the influences of various antiestrogens such as MER-25, progesterone and testosterone. MER-25 markedly inhibited the estrogen-stimulated vaginal TTC reduction when administered simultaneously, but the inhibition was reduced or abolished according to the injection interval between estradiol and MER-25 being prolonged for 3, 6 or 12 hrs. Progesterone and testosterone, however, produced almost consistent inhibition without regard to the time of administration within a period of 12 hrs. after the estrogen injection. Histological investigations on the vaginal epithelium also demonstrated that MER-25 almost completely blocked an earlier response to estrogen, primary proliferation of epithelial cells, while progesterone and testosterone allowed the epithelial proliferation in a relatively normal manner. These results indicate that MER-25 only inhibits earlier step of estrogen action, whereas either progesterone or testosterone inhibits rather later stage. It is found that there is close correlation between the ability of formazan production in the superficial cells and differentiation of vaginal epithelium under influences of these anti-estrogenic substances, supporting the previous explanation for the mechanism of hormonal regulation of vaginal TTC reduction.