Estrogen receptor-beta gene disruption potentiates estrogen-inducible aggression but not sexual behaviour in male mice.
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.
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ABSTRACT: Estrogens play a salient role in the development and maintenance of both male and female nervous systems and behaviors. The plainfin midshipman (Porichthys notatus), a teleost fish, has two male reproductive morphs that follow alternative mating tactics and diverge in multiple somatic, hormonal and neural traits, including the central control of morph-specific vocal behaviors. After we identified duplicate estrogen receptors (ERβ1 and ERβ2) in midshipman, we developed antibodies to localize protein expression in the central vocal-acoustic networks and saccule, the auditory division of the inner ear. As in other teleost species, ERβ1 and ERβ2 were robustly expressed in the telencephalon and hypothalamus in vocal-acoustic and other brain regions shown previously to exhibit strong expression of ERα and aromatase (estrogen synthetase, CYP19) in midshipman. Like aromatase, ERβ1 label co-localized with glial fibrillary acidic protein (GFAP) in telencephalic radial glial cells. Quantitative PCR revealed similar patterns of transcript abundance across reproductive morphs for ERβ1, ERβ2, ERα and aromatase in the forebrain and saccule. In contrast, transcript abundance for ERs and aromatase varied significantly between morphs in and around the sexually polymorphic vocal motor nucleus (VMN). Together, the results suggest that VMN is the major estrogen target within the estrogen-sensitive hindbrain vocal network that directly determines the duration, frequency and amplitude of morph-specific vocalizations. Comparable regional differences in steroid receptor abundances likely regulate morph-specific behaviors in males and females of other species exhibiting alternative reproductive tactics. J. Comp. Neurol., 2013. © 2013 Wiley Periodicals, Inc.The Journal of Comparative Neurology 03/2013; · 3.66 Impact Factor
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ABSTRACT: Testosterone is known to play an important role in the regulation of male-type sexual and aggressive behavior. As an aromatised metabolite of testosterone, estradiol-induced activation of estrogen receptor α (ERα) may be crucial for the induction of these behaviors in male mice. However, the importance of ERα expressed in different nuclei for this facilitatory action of testosterone has not been determined. To investigate this issue, we generated an adeno-associated virus vector expressing a small hairpin RNA targeting ERα to site-specifically knockdown ERα expression. We stereotaxically injected either a control or ERα targeting vector into the medial amygdala, medial pre-optic area (MPOA), or ventromedial nucleus of the hypothalamus (VMN) in gonadally intact male mice. Two weeks after injection, all mice were tested biweekly for sexual and aggressive behavior, alternating between behavior tests each week. We found that suppressing ERα in the MPOA reduced sexual but not aggressive behavior, whereas in the VMN it reduced both behaviors. Knockdown of ERα in the medial amygdala did not alter either behavior. Additionally, it was found that ERα knockdown in the MPOA caused a parallel reduction in the number of neuronal nitric oxide synthase-expressing cells. Taken together, these results indicate that the testosterone facilitatory action on male sexual behavior requires the expression of ERα in both the MPOA and VMN, whereas the testosterone facilitatory action on aggression requires the expression of ERα in only the VMN.European Journal of Neuroscience 01/2013; · 3.75 Impact Factor
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ABSTRACT: Estrogenic functions in regulating behavioral states such as motivation, mood, anxiety, and cognition are relatively well documented in female humans and animals. In males, however, although the entire enzymatic machinery for producing estradiol and the corresponding receptors are present, estrogenic functions have been largely neglected. Therefore, and as a follow-up study to previous research, we sub-chronically applied a specific estrogen receptor α (ERα) antagonist in young male rats before and during a spatial learning task (holeboard). The male rats showed a dose-dependent increase in motivational, but not cognitive, behavior. The expression of hippocampal steroid receptor genes, such as glucocorticoid (GR), mineralocorticoid (MR), androgen (AR), and the estrogen receptor ERα but not ERβ was dose-dependently reduced. The expression of the aromatase but not the brain-derived neurotrophic factor (BDNF) encoding gene was also suppressed. Reduced gene expression and increased behavioral performance converged at an antagonist concentration of 7.4 µmol. The hippocampal and blood serum hormone levels (corticosterone, testosterone, and 17β-estradiol) did not differ between the experimental groups and controls. We conclude that steroid receptors (and BDNF) act in a concerted, network-like manner to affect behavior and mutual gene expression. Therefore, the isolated view on single receptor types is probably insufficient to explain steroid effects on behavior. The steroid network may keep motivation in homeostasis by supporting and constraining the behavioral expression of motivation.PLoS ONE 01/2013; 8(11):e79303. · 3.73 Impact Factor