Treatment with the specific estrogen receptor antagonist ICI 182,780 demasculinizes neuron soma size in the developing zebra finch brain

Abstract In zebra finches, many features of the neural song system are more pronounced in males compared to females. The exact mechanism(s) responsible for these differences are unknown, but may involve steroid hormones. More specifically, estrogens are most effective in masculinizing the female brain. Attempts to prevent masculine development through various estrogen receptor antagonists have been relatively ineffective, possibly due to partial agonistic activity of the compounds tested. To further investigate the role of estrogens in dimorphic development we utilized a more potent estrogen receptor blocker, ICI 182,780. Animals were treated during the first 25 days post-hatching. Daily intracranial injections significantly decreased neuron soma size in RA and HVC of both sexes. A similar effect was noted in LMAN. Treatment also appeared to decrease the volume of several song control nuclei. Together, these data support the hypothesis that ICI is an effective estrogen receptor antagonist in the zebra finch brain and that estrogens may influence sexually dimorphic development of the zebra finch song circuit. However, reported inconsistencies about sex differences in estrogen exposure and/or utilization exist, suggesting that complete sexual differentiation and development likely involve additional factors.