The effects of an aromatase inhibitor and a 5 alpha-reductase inhibitor upon the occurrence of polyovular follicles, persistent anovulation, and permanent vaginal stratification in mice treated neonatally with testosterone

Female C57BL/Tw mice were given 5 daily injection of 20 micrograms testosterone (T), 100 micrograms 4-hydroxy-4-androstene-3, 17-dione (4-HA), 100 micrograms 6-methylene-4-pregnene-3, 20-dione (6-MP), 4-HA + 6-MP, T + 4-HA, T + 6-MP, and T + 4-HA + 6-MP starting on the day of birth. The animals were ovariectomized at 30 days or 90 days of age and were killed at 150 days. The incidence of polyovular follicles (PF) at 30 days of age was significantly increased by neonatal treatment with T. By contrast, the PF incidence was significantly reduced by injections of 4-HA given simultaneously with T. Neonatally T- or T + 6-MP-treated 90-day-old mice had ovaries containing follicles and hypertrophied interstitial cells but no corpora lutea. By contrast, T + 4-HA (64%)- and T + 4-HA + 6-MP (82%)-treated mice had ovaries with corpora lutea. In the T + 4-HA + 6-MP (82%)-treated mice had ovaries with corpora lutea. In the T + 4-HA + 6-MP-treated, 150-day-old, ovariectomized mice, the number of mice showing vaginal epithelial stratification was significantly decreased as compared with T-treated mice. There were no significant differences in the number of layers, thickness, and mitotic rate of vaginal epithelium of T-treated mice compared with mice treated with T + 4-HA, T + 6-MP, or T + 4-HA + 6-MP. The present results indicate that development of PF and persistent anovulation are due to the direct action of estrogen (E) derived from T upon neonatal ovarian follicles and the neonatal hypothalamo-hypophysial system, and that T itself can induce ovary-independent vaginal changes, although 5 alpha-reduced androgen and estrogen derived from T seem to be more effective in this regard.