Genotype/Age Interactions on Aggressive Behavior in Gonadally Intact Estrogen Receptor β Knockout (βERKO) Male Mice

Nomura, Masayoshi; Durbak, Larissa; Chan, Johnny S.W.; Smithies, Oliver; Gustafsson, Jan Åke; Korach, Kenneth S.; Pfaff, Donald W.; Ogawa, Sonoko

doi:10.1006/hbeh.2002.1773

Cited by 145 publications

(86 citation statements)

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“…This reduction is unlikely to be due to changes in male testosterone levels in that in previous studies it was shown that exposure to the odors of a novel female blunted predator-odor-induced rises in corticosterone levels, but was not associated with an immediate increase in testosterone levels . The impairments of the KO mice also cannot be attributed to differences in basal testosterone levels in that the various WTs and KOs examined here are reported to display similar basal testosterone levels (Ogawa et al, 1998Nomura et al, 2002Nomura et al, , 2006. Furthermore, increases in testosterone levels in male mice generally occur 15-30 min after exposure to females or their odors (Coquelin and Desjardins, 1982;Smith et al, 1996; suggesting that the emboldening responses seen 1 min after exposure to female odor are not directly associated with changes in testosterone.…”

Section: Discussionmentioning

confidence: 64%

“…Regarding the social recognition, female αERKO and βERKO mice have also been shown to differ in the extent of their attenuation of social memory . In addition, αERKO males displayed reduced aggressive behavior towards other males while βERKO males displayed enhanced inter-male aggressiveness relative to their WTs (Ogawa et al, 1998(Ogawa et al, , 2000Imwalle et al, 2002;Nomura et al, 2002;Rissman et al, 1999;Scordalakes and Rissman, 2003;Dominguez-Salazar et al, 2004). In this regard, it has been suggested that ERβ activation may exert an attenuating effect on male aggression induced by estrogen through ERα-mediated mechanisms (Nomura et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to ERα, the lack of a functional ERβ, while affecting social recognition , did not impair normal expression of adult sexual behavior or preferences for females by male mice. Both the wild-type (βERWT) and βERKO male mice expressed an interest in, and responses to, female olfactory cues and exhibited normal sexual behavior, with the βERKO mice also displaying enhanced inter-male aggression (Ogawa et al, 1999(Ogawa et al, , 2000Nomura et al, 2002). Thus, ERα seems to be involved in the mediation of both social responses and sexual behaviors, while ERβ seems to be involved with social responses but not sexual behaviors.…”

Section: Introductionmentioning

confidence: 99%

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Estrogen receptors α and β mediate different aspects of the facilitatory effects of female cues on male risk taking

Kavaliers

Devidze

Choleris

et al. 2008

Psychoneuroendocrinology

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SummaryMale risk taking and decision making are affected by sex-related cues, with men making poorer and riskier decisions in the presence of females and, or their cues. In non-human species, female cues can also increase male risk taking, reducing their responses to predator threat. As estrogen receptors α and β (ERα and ERβ) are involved in the mediation of social and sexual responses, we investigated their roles in determining the effects of female-associated cues on male risk taking. We examined the effects of brief pre-exposure to the odors of either a novel or familiar estrous female on the avoidance of, and aversive responses to, predator threat (cat odor) in ERα and ERβ wild type (αERWT, βERWT) and gene-deleted (knockout, αERKO, βERKO) male mice. Exposure of αERWT and βERWT males to the odors of a novel, but not a familiar, estrous female mouse resulted in enhanced risk taking with the males displaying reduced avoidance of, and analgesic responses to, cat odor. In contrast, αERKO male mice failed to show any changes in risk taking, while βERKO males, although displaying greater risk taking, did not distinguish between novel and familiar females, displaying similarly reduced avoidance responses to cat odor after exposure to either a novel or familiar female odor. These findings indicate that the gene for ERα is associated with the sexual mechanisms (response to estrous female) and the genes for ERβ and ERα with the social (recognition of novel female) mechanisms underlying the effects of female cues on male risk taking. *Corresponding author. kavalier@uwo.ca (M. Kavaliers).

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Estrogen receptors α and β mediate different aspects of the facilitatory effects of female cues on male risk taking

Kavaliers

Devidze

Choleris

et al. 2008

Psychoneuroendocrinology

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“…[59][60][61] Thus, the lack of social recognition by ER-b knockout mice 62 could explain the hyperaggressiveness displayed by ER-b knockout male mice. 63 Altogether, these data invoke the idea of a four-gene micronet important for social behaviors (Figure 2).…”

Section: Anxiety Reductionmentioning

confidence: 66%

Hormonal symphony: steroid orchestration of gene modules for sociosexual behaviors

Mong

Pfaff

2004

Mol Psychiatry

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Genes induced by estrogens in the mammalian forebrain influence a variety of neural functions. Among them, reproductive behavior mechanisms are very well understood. Their functional genomics provide a theoretical paradigm for linking genes to neural circuits to behavior. We propose that estrogen-induced genes are organized in modules: Growth of hypothalamic neurons; Amplification of the estrogen effect by progesterone; Preparative behaviors; Permissive actions on sex behavior circuitry; and Synchronization of mating behavior with ovulation. These modules may represent mechanistic routes for CNS management of successful reproduction. Moreover, new microarray results add estrogen-dependent genes, including some expressed in glia, suggesting possible hormone-dependent neuronal/ glial coordination. Molecular Psychiatry (2004) 9, 550-556. doi:10.1038/sj.mp.4001493Keywords: sex; estrogen; gene; hypothalamus; lordosis; arousal; noradrenalin; acetylcholine; oxytocin; enkephalin; opioid; GnRH; LHRH; neurotrophic; anxiety Sexual behaviors are important for psychiatry. Not only hypersexual disorders but also concerns about lack of sexual desire are prominent, internationally, in the psychiatric landscape. Further, in some traditions of psychiatric theory, sexual problems are held to be at the root of apparently unrelated syndromes. Finally, biological thought has held that sexual affiliations provide the bauplan, the structural precedent, for a wide variety of other social relations, both normal or abnormal. Fortunately, the molecular analysis of stereotyped sexual behaviors has benefited greatly from several strategic advantages: Even in mammals, simple stimuli and responses permit neural net analysis. Steroid hormones acting through nuclear receptors which are transcription factors invoke regulated gene expression, for example, in hypothalamic neurons.1 In turn, these neurons control mating behavior circuits.Drawing hormone-regulated gene expression into the explanation of mammalian sex behavior has proceeded rapidly. Here we theoretically propose a gene network-really, a micronet-downstream of estrogen action in the forebrain responsible for courtship and lordosis behavior in females. Not a massive review of the literature or an original data report, this paper comprises an attempt to draw different transcriptional systems into a new theoretical formulation. These efforts to explain hormone-driven behaviors have benefited from Rosenfeld's example of genetic network control over pituitary gland development.2 Both direct and indirect causal routes are depicted below.Causal routes, downstream from genomic action; a modular system emergent The primary sex behavior of female quadrupeds, lordosis, depends on defined physical signals: cutaneous stimuli and estrogens þ progestins 1 (E þ P). The neural circuit has been worked out; estrogen-dependent transcription in ventromedial hypothalamic cells allows permissive signals to the midbrain central gray, thus enabling the rest of the circuit. In the absence of fear or anxiety-pro...

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“…However, when adult wt and Tfm male mice were castrated and supplemented with exogenous E2, they showed similar levels of aggression, indicating that low levels of circulating testicular hormones, and not dysfunctional ARs, underlies decreased aggression in gonadally intact Tfm male mice (Scordalakes and Rissman, 2004). Studies using hormone receptor knockout mice also indicate that aggression may be mostly, if not entirely, mediated through activation of estrogen receptors, with enhancement of aggression via ERα activation and inhibition via ERβ activation (Scordalakes and Rissman, 2004;Nomura et al, 2002). …”

mentioning

confidence: 99%

The role of androgen receptors in the masculinization of brain and behavior: What we've learned from the testicular feminization mutation

Zuloaga

Puts

Jordan

et al. 2008

Hormones and Behavior

213

156

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Many studies demonstrate that exposure to testicular steroids such as testosterone early in life masculinizes the developing brain, leading to permanent changes in behavior. Traditionally, masculinization of the rodent brain is believed to depend on estrogen receptors (ERs) and not androgen receptors (ARs). According to the aromatization hypothesis, circulating testosterone from the testes is converted locally in the brain by aromatase to estrogens, which then activate ERs to masculinize the brain. However, an emerging body of evidence indicates that the aromatization hypothesis cannot fully account for sex differences in brain morphology and behavior, and that androgens acting on ARs also play a role. The testicular feminization mutation (Tfm) in rodents, which produces a nonfunctional AR protein, provides an excellent model to probe the role of ARs in the development of brain and behavior. Tfm rodent models indicate that ARs are normally involved in the masculinization of many sexually dimorphic brain regions and a variety of behaviors, including sexual behaviors, stress response and cognitive processing. We review the role of ARs in the development of the brain and behavior, with an emphasis on what has been learned from Tfm rodents as well as from related mutations in humans causing complete androgen insensitivity. Keywordscomplete androgen insensitivity syndrome -CAIS; vasopressin; anxiety; spatial memory; bed nucleus; medial amygdala; SDN-POA; sexual behavior; aggression; VMH Exposure to testicular steroids such as testosterone (T) early in life masculinizes the developing brain, leading to permanent changes in behavior in a wide variety of animal models (Morris et al., 2004). According to the aromatization hypothesis, T is converted by aromatase into 17-β estradiol (E2), which then acts on estrogen receptors (ERs) to masculinize the brain (Naftolin et al., 1975). Traditionally, aromatization is believed to be the mechanism by which the rodent brain becomes masculinized and defeminized. Some sexually dimorphic regions within the hypothalamus adhere well to this hypothesis, including the sexually dimorphic nucleus of the preoptic area (SDN-POA) and anteroventral periventricular nucleus (AVPV). T spares neuronsCorresponding author: Damian Zuloaga, Neuroscience Program, 108 Giltner Hall, Michigan State University, East Lansing, MI 48824, Phone: Fax: (517) 432-2744, Email: E-mail: zuloagad@msu.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript from death in the SDN-POA...

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Genotype/Age Interactions on Aggressive Behavior in Gonadally Intact Estrogen Receptor β Knockout (βERKO) Male Mice

Cited by 145 publications

References 36 publications

Estrogen receptors α and β mediate different aspects of the facilitatory effects of female cues on male risk taking

Estrogen receptors α and β mediate different aspects of the facilitatory effects of female cues on male risk taking

Hormonal symphony: steroid orchestration of gene modules for sociosexual behaviors

The role of androgen receptors in the masculinization of brain and behavior: What we've learned from the testicular feminization mutation

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