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eNeuro. 2016 Mar 31;3(2). pii: ENEURO.0155-15.2016. doi: 10.1523/ENEURO.0155-15.2016. eCollection 2016 Mar-Apr.

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.

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Laboratory of Behavioral Neuroendocrinology, University of Tsukuba , Tsukuba, Ibaraki 305-8577, Japan.
Laboratory of Molecular Neurosurgery, Weill Cornell University Medical College , New York, New York 10021.
Department of Pharmacology, School of Medicine, Aichi Medical University , Nagakute, Aichi 480-1195, Japan.
Department of Psychology, Kyoto Tachibana University , Kyoto, Kyoto 607-8175, Japan.


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. Prepubertal 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. Because βERKD in the MPOA only in adulthood did not affect either sexual or aggressive behaviors, it was concluded that pubertal ERβ 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 βERKD in the MeA had any effects on sexual and aggressive behavior, βERKD in adulthood disrupted sexual preference of receptive females over nonreceptive 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.


aggressive behavior; estrogen receptor β; medial amygdale; medial preoptic area; sexual preference; site-specific knockdown

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