Antiestrogens fail to prevent the masculine ontogeny of the zebra finch song system.

Early treatment with the antiestrogen, tamoxifen, fails to block the ontogeny of the male zebra finch song system which is hypothesized to occur as a result of early estradiol action. In Experiment 1, two other antiestrogens, LY117018 or CI628, or vehicle was administered daily to zebra finch chicks for the first 20 days after hatching at which time the males were castrated. Comparisons of experimental and control brains at 60 days revealed that neither antiestrogen prevented the masculinization of the song system in males. Rather, both compounds increased (hypermasculinized) neuronal soma area in male MAN (magnocellular nucleus of the anterior neostriatum), DLRA (dorsolateral portion of the robust nucleus of the archistriatum), and in HVc (caudal nucleus of the ventral hyperstriatum). In females both compounds masculinized by increasing neuronal soma area in HVc and inducing the formation of Area X. Experiment 2 showed that neither LY117018 nor CI628 was effective in preventing the masculinization of the song system typical of 25-day-old males when administered daily from hatching until sacrifice. Rather, both compounds masculinized females by inducing the formation of Area X, and LY117018 increased RA volume. LY117018 hypermasculinized males by increasing HVc volume and size of neuronal somata in MAN, HVc, and DLRA. CI628 also hypermasculinized males by increasing RA volume and neuronal soma size in HVc and RA. The failure of the present compounds to block masculinization of the song system and the paradox of hypermasculinization by antiestrogens are discussed with reference to the estradiol-masculinization hypothesis.