Genotype/age interactions on aggressive behavior in gonadally intact estrogen receptor β knockout (βERKO) male mice

Estrogen, as an aromatized metabolite of testosterone, has a facilitatory effect on male aggressive behavior in mice. Two subtypes of estrogen receptors, α (ER-α) and β (ER-β), in the brain are known to bind estrogen. Previous studies revealed that the lack of ER-α gene severely reduced the induction of male aggressive behavior. In contrast, mice that lacked the ER-β gene tended to be more aggressive than wild type (WT) control mice, although the behavioral effects of ER-β gene disruption were dependent on their social experience. These findings lead us to hypothesize that estrogen may facilitate aggression via ER-α whereas it may inhibit aggression via ER-β. In the present study, we further investigated the role of ER-β in the regulation of aggressive behavior by examining developmental changes starting at the time of first onset, around the age of puberty. Aggressive behaviors of ER-β gene knockout (βERKO) mice were examined in three different age groups, puberty, young-adult, and adult. Each mouse was tested every other day for three times in a resident-intruder paradigm against olfactory bulbectomized intruder mice and their trunk blood was collected for measurements of serum testosterone after the completion of the study. Overall, βERKO mice were significantly more aggressive than WT. These genotype differences were more pronounced in puberty and young adult age groups, but not apparent in the adult age group, in which βERKO mice were less aggressive than those in two younger age groups. Serum testosterone levels of βERKO mice were significantly higher than those of WT mice only in the pubertal age group, but not in young adult (when βERKO mice were still significantly more aggressive than WT mice) and adult (when no genotype differences in aggression were found) age groups. These results suggest that ER-β mediated actions of gonadal steroids may more profoundly be involved in the inhibitory regulation of aggressive behavior in pubertal and young adult mice.