The sexually dimorphic expression of L7/SPA, an estrogen receptor coactivator, in zebra finch telencephalon.

Sex differences in the zebra finch (Taeniopygia guttata) brain are robust and include differences in morphology (song control nuclei in males are significantly larger) and behavior (only males sing courtship songs). In zebra finches, hormonal manipulations during development fail to reverse sex differences in song nuclei size and suggest that the classical model of sexual differentiation is incomplete for birds. Coactivators act to initiate transcriptional activity of steroid receptors, and may help explain why hormonal manipulations alone are not sufficient to demasculinize the male zebra finch brain. The present study investigated the expression and localization of L7/SPA (an estrogen receptor coactivator) mRNA and protein expression across the development of zebra finch song nuclei from males and females collected on P1 (song nuclei not yet formed), P10 (posthatch day 10, song nuclei formed), P30 (30 days posthatch, sexually immature but song nuclei formed and birds learning to sing), and adult birds (older than 65 days and sexually mature). Northern blot analysis showed a significant sex difference in P1 and adult L7/SPA mRNA expression while Western blot analysis also showed enhanced expression in the male brain at all age points. Both in situ hybridization and immunohistochemistry demonstrated that L7/SPA mRNA and protein were located in the song nuclei as well as expressed globally. Elevated coactivator expression may be a possible mechanism controlling the development of male song control nuclei, and coactivators such as L7/SPA may be important regulators of the masculinizing effects of estradiol on brain sexual differentiation.