Tamoxifen's effects on the zebra finch song system are estrogenic, not antiestrogenic

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Abstract
Antiestrogens fail to block the masculine ontogeny of the zebra finch song system that is hypothesized to occur as a result of early estrogen action. Moreover, they hypermasculinize the male, and masculinize the female song systems. In experiment 1, we assessed whether these antiestrogenic effects might mimic estrogenic actions. Zebra finch chicks received one of two treatments. They were given estradiol benzoate (EB) or vehicle daily for the first 20 days after hatching and sacrificed at 60 days of age, or they received EB or vehicle for the first 25 days after hatching, at which time they were sacrificed. In the day 60 group, certain attributes of the song system were hypermasculinized in males and masculinized in females by EB, when compared with controls. In the day 25 group, males treated with EB were partially demasculinized, while the females were partially masculinized. In experiment 2, we assessed whether simultaneous treatment with tamoxifen was capable of antagonizing the effects of EB obtained in experiment 1 (day 60 group). Sixty-day-old females, previously treated with both EB and tamoxifen for the first 20 days after hatching, had more masculine song regions than females treated with either EB alone or tamoxifen alone. In males, the effects of the combined treatment of EB and tamoxifen over those produced by tamoxifen alone were not as dramatic as in the female. These results are similar to those obtained in systems where tamoxifen is purely estrogenic and suggest that in the song system, tamoxifen acts as an estrogen, not an antiestrogen.