Estrogen receptor-beta gene disruption potentiates estrogen-inducible aggression but not sexual behaviour in male mice.

Laboratory of Neurobiology and Behaviour, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
European Journal of Neuroscience (Impact Factor: 3.75). 05/2006; 23(7):1860-8. DOI: 10.1111/j.1460-9568.2006.04703.x
Source: PubMed

ABSTRACT Aggressive behaviour of gonadally intact male mice is increased by estrogen receptor (ER)-beta gene disruption, whereas sexual behaviour remains unchanged. The elevated aggression levels following ER-beta 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-beta activation in the regulation of aggressive and sexual behaviour were investigated in gonadectomized ER-beta knockout (betaERKO) and wild-type (WT) male mice treated with various doses of estrogen. Overall, estradiol benzoate (EB) treatment induced higher levels of aggression in betaERKO mice than in WT mice. In WT mice, the levels of aggression induced by EB were highest in the lowest-dose (2.5 microg/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 betaERKO mice. A marked genotype difference in dose responses is inferred, such that the ER-alpha-mediated facilitatory action of estrogen is more pronounced at lower and physiological doses and the ER-beta-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 betaERKO and WT at either dose of EB (2.5 and 12.5 microg/day) examined. These findings support the notion that ER-beta activation may exert an attenuating action on male aggression induced by estrogen through ER-alpha-mediated brain mechanisms, whereas its effect on male sexual behaviour is relatively small.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Gonadal hormones mediate both affiliative and agonistic social interactions. Research in estrogen receptor alpha (ERα) or beta (ERβ) knockout (KO) mice suggests that ERα increases and ERβ decreases male aggression, while the opposite is found for female ERαKO and ERβKO mice. Using a detailed behavioural analysis of the resident-intruder test, we have shown that the ERβ selective agonist WAY-200070 increased agonistic behaviours, such as aggressive grooming and pushing down a gonadectomized (gonadex) intruder, in gonadally intact but not gonadex male and female resident mice, while leaving attacks unaffected. The role of acute activation of ERα in agonistic behaviour in adult non-KO CD1 mice is presently unknown. The current study assesses the effects of the ERα selective agonist 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) on the social and agonistic responses of gonadally intact and gonadex male and female CD1 mice to a gonadex, same-sex intruder. PPT had few effects in gonadally intact mice, but seems to increase sex-typical aggression (i.e., attacks in males, other dominance-related behaviours in females) in gonadex mice. In untreated mice, we confirmed our previous findings that gonadally intact males attacked the intruder more than females, but females spent more time engaged in agonistic behaviour than males. As in our previous results, we observed that gonadex mice generally show behaviour patterns more like those of the gonadally intact opposite sex, while leaving overall levels of agonistic behaviour unaffected. Taken together, our current and previous results show that exogenous activation of ERα had no effects in gonadally intact mice, but increased sex-typical agonistic behaviour in gonadex mice, while ERβ had no effects in gonadex mice, but increased non-attack agonistic behaviour in gonadally intact animals. This suggests that, as in social recognition, ERα may be necessary for the activation of agonistic responses, while ERβ may play a modulatory role.
    Psychoneuroendocrinology 01/2011; 36(7):981-95. · 5.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: New cubic cage-like mesoporous materials with a bulky N-heterocyclic carbene [IPr, 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene] precursor in the framework were synthesized by a co-condensation of IPr precursor-bridged organosilane and TEOS in the presence of template. N2 sorption, XRD and TEM characterizations revealed that the mesostructural orderings of the synthesized materials depended on the molar fraction of the bridged organosilane in the initial gel mixture. With the increase in the molar fraction of the organosilane from 2.5% to 15%, the mesostructure of the synthesized material changed from a well-ordered 3D ordered structure to a amorphous structure. FT-IR and solid-state NMR characterizations confirmed that IPr carbene precursor was covalently integrated with the solid materials. Such hybrid materials were able to coordinate Pd(acac)2, leading to active solid catalysts for Suzuki–Miyaura couplings of less reactive aryl chlorides. The solid catalyst could be reused 8 times without a significant decrease in activity. Furthermore, the solid catalyst was active for the coupling of C(sp3)-chlorides and arylboronic acids.
    Journal of Catalysis. 01/2010; 276(1):123-133.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Maternal separation (MS) is an animal model mimicking the effects of early life stress on the development of emotional and social behaviors. Recent studies revealed that MS stress increased social anxiety levels in female mice and reduced peri-pubertal aggression in male mice. Estrogen receptor (ER) β plays a pivotal role in the regulation of stress responses and anxiety-related and social behaviors. Behavioral studies using ERβ knockout (βERKO) mice reported increased social investigation and decreased social anxiety in βERKO females, and elevated aggression levels in βERKO males compared to wild-type (WT) mice. In the present study, using βERKO and WT mice, we examined whether ERβ contributes to MS effects on anxiety and social behaviors. βERKO and WT mice were separated from their dam daily (4 h) from postnatal day 1-14 and control groups were left undisturbed. First, MS and ERβ gene deletion individually increased anxiety-related behaviors in the open field test, but only in female mice. Anxiety levels were not further modified in βERKO female mice subjected to MS stress. Second, βERKO female mice showed higher levels of social investigation compared with WT in the social investigation test and long-term social preference test. However, MS greatly reduced social investigation duration and elevated number of stretched approaches in WT and βERKO females in the social investigation test, suggesting elevated levels of social anxiety in both genotypes. Third, peri-pubertal and adult βERKO male mice were more aggressive than WT mice as indicated by heightened aggression duration. On the other hand, MS significantly decreased aggression duration in both genotypes, but only in peri-pubertal male mice. Altogether, these results suggest that βERKO mice are sensitive to the adverse effects of MS stress on subsequent female and male social behaviors, which could then have overrode the ERβ effects on female social anxiety and male aggression.
    Frontiers in neuroscience. 01/2014; 8:274.