• androgen receptor;
  • knockout mouse;
  • estrogen receptor α;
  • sex difference;
  • testosterone


Aggressive behaviour of gonadally intact male mice is increased by estrogen receptor (ER)-β gene disruption, whereas sexual behaviour remains unchanged. The elevated aggression levels following ER-β gene disruption is pronounced during repeated aggression tests in young animals and the first aggression test in adults. In the present study, the roles of ER-β activation in the regulation of aggressive and sexual behaviour were investigated in gonadectomized ER-β knockout (βERKO) and wild-type (WT) male mice treated with various doses of estrogen. Overall, estradiol benzoate (EB) treatment induced higher levels of aggression in βERKO mice than in WT mice. In WT mice, the levels of aggression induced by EB were highest in the lowest-dose (2.5 µg/day) group and gradually decreased in higher-dosage groups. On the other hand, equally high levels of aggressive behaviour were induced by all three doses of EB in βERKO mice. A marked genotype difference in dose responses is inferred, such that the ER-α-mediated facilitatory action of estrogen is more pronounced at lower and physiological doses and the ER-β-mediated inhibitory action is only unveiled at higher doses of estrogen. In contrast to aggression, the levels of sexual behaviour induced by EB were not different between βERKO and WT at either dose of EB (2.5 and 12.5 µg/day) examined. These findings support the notion that ER-β activation may exert an attenuating action on male aggression induced by estrogen through ER-α-mediated brain mechanisms, whereas its effect on male sexual behaviour is relatively small.