TY - JOUR T1 - Effects of pre-pubertal or adult site-specific knockdown of estrogen receptor β in the medial preoptic area and medial amygdala on social behaviors in male mice JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0155-15.2016 SP - ENEURO.0155-15.2016 AU - Mariko Nakata AU - Kazuhiro Sano AU - Sergei Musatov AU - Naoko Yamaguchi AU - Toshiro Sakamoto AU - Sonoko Ogawa Y1 - 2016/03/23 UR - http://www.eneuro.org/content/early/2016/03/23/ENEURO.0155-15.2016.abstract N2 - Testosterone, after being converted to estradiol in the brain, acts on estrogen receptors (ERα and ERβ) and controls the expression of male-type social behavior. Previous studies in male mice have revealed that ERα expressed in the medial preoptic area (MPOA) and medial amygdala (MeA) are differently involved in the regulation of sexual and aggressive behaviors by testosterone action at the time of testing in adult and/or on brain masculinization process during pubertal period. However, a role played by ERβ in these brain regions still remains unclear. Here we examined the effects of site-specific knockdown of ERβ (βERKD) in the MPOA and MeA on male social behaviors with the use of adeno-associated viral mediated RNA interference methods in ICR/Jcl mice. Pre-pubertal βERKD in the MPOA revealed that continuous suppression of ERβ gene expression throughout the pubertal period and adulthood decreased aggressive but not sexual behavior tested as adults. Since βERKD in the MPOA only in adulthood did not affect either sexual or aggressive behaviors, it was concluded that pubertal ERβ in the MPOA may have an essential role for the full expression of aggressive behavior in adulthood. On the other hand, although neither pre-pubertal nor adult βERKD in the MeA had any effects on sexual and aggressive behavior, βERKD in adulthood disrupted sexual preference of receptive females over non-receptive females. Collectively, these results suggest that ERβ in the MPOA and MeA are involved in the regulation of male sexual and aggressive behavior in a manner substantially different from that of ERα.Significance Statement: We investigated the role played by estrogen receptor β (ERβ) expressed in the medial preoptic area (MPOA) and medial amygdala (MeA) in the regulation of male-type social behaviors with the use of RNA interference methods for brain site-specific ERβ knockdown (βERKD) in mice. We found that ERβ in the MPOA may be necessary for testosterone to fully masculinize the aggressive, but not sexual, behavior neural network through organizational action during the pubertal period. On the other hand, ERβ in the MeA may be involved in sexual information processing since βERKD male mice failed to show sexual preference toward a receptive female over a non-receptive female. These finding are greatly contrasted with previously reported functions of ERα. ER -