Pubertal activation of estrogen receptor a in the medial amygdala is essential for the full expression of male social behavior in mice
Significance Testosterone stimulation during the pubertal period is necessary for the full expression of male type social behaviors. However, it is not known whether estrogen receptor (ER) a may be involved in pubertal organizational action of testosterone on the regulation of male type social behaviors. In this study, we showed that the prepubertal knockdown of ERa in the medial amygdala (MeA) of gonadally intact male mice reduced both sexual and aggressive behaviors as well as the number of MeA neurons later in adulthood. These results indicate that not only aromatization but also ERa expression in the MeA during the pubertal period is required for organizational action of testosterone to fully masculinize neural circuitry responsible for the expression of male type social behaviors. Testosterone plays a central role in the facilitation of male type social behaviors, such as sexual and aggressive behaviors, and the development of their neural bases in male mice. The action of testosterone via estrogen receptor (ER) a, after being aromatized to estradiol, has been suggested to be crucial for the full expression of these behaviors. We previously reported that silencing of ERa in adult male mice with the use of a virally mediated RNAi method in the medial preoptic area (MPOA) greatly reduced sexual behaviors without affecting aggressive behaviors whereas that in the medial amygdala (MeA) had no effect on either behavior. It is well accepted that testosterone stimulation during the pubertal period is necessary for the full expression of male type social behaviors. However, it is still not known whether, and in which brain region, ERa is involved in this developmental effect of testosterone. In this study, we knocked down ERa in the MeA or MPOA in gonadally intact male mice at the age of 21 d and examined its effects on the sexual and aggressive behaviors later in adulthood. We found that the prepubertal knockdown of ERa in the MeA reduced both sexual and aggressive behaviors whereas that in the MPOA reduced only sexual, but not aggressive, behavior. Furthermore, the number of MeA neurons was reduced by prepubertal knockdown of ERa. These results indicate that ERa activation in the MeA during the pubertal period is crucial for male mice to fully express their male type social behaviors in adulthood.
Proceedings of the National Academy of Sciences