Effects of Prepubertal or Adult Site-Specific Knockdown of Estrogen Receptor β in the Medial Preoptic Area and Medial Amygdala on Social Behaviors in Male Mice

Testosterone, after being converted to estradiol in the brain, acts on estrogen receptors (ER alpha and ER beta) and controls the expression of male-type social behavior. Previous studies in male mice have revealed that ER alpha 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 ER beta in these brain regions still remains unclear. Here we examined the effects of site-specific knockdown of ER beta (beta ERKD) in the MPOA and MeA on male social behaviors with the use of adeno-associated viral mediated RNA interference methods in ICR/Jcl mice. Prepubertal beta ERKD in the MPOA revealed that continuous suppression of ER beta gene expression throughout the pubertal period and adulthood decreased aggressive but not sexual behavior tested as adults. Because beta ERKD in the MPOA only in adulthood did not affect either sexual or aggressive behaviors, it was concluded that pubertal ER beta in the MPOA might have an essential role for the full expression of aggressive behavior in adulthood. On the other hand, although neither prepubertal nor adult beta ERKD in the MeA had any effects on sexual and aggressive behavior, beta ERKD in adulthood disrupted sexual preference of receptive females over nonreceptive females. Collectively, these results suggest that ER beta in the MPOA and MeA are involved in the regulation of male sexual and aggressive behavior in a manner substantially different from that of ER alpha