Estrogen receptors in the medial amygdala inhibit the expression of male prosocial behavior
Open accessAbstract
Studies using estrogen receptor α (ERα) knock-out mice indicate that ERα masculinizes male behavior. Recent studies of ERα and male prosocial behavior have shown an inverse relationship between ERα expression in regions of the brain that regulate social behavior, including the medial amygdala (MeA), and the expression of male prosocial behavior. These studies have lead to the hypothesis that low levels of ERα are necessary to “permit” the expression of high levels of male prosocial behavior. To test this, viral vectors were used to enhance ERα in male prairie voles (Microtus ochrogaster), which display high levels of prosocial behavior and low levels of MeA ERα. Adult male prairie voles were transfected with ERα in the MeA (MeA-ERα) or the caudate–putamen (ERα control) or luciferase (MeA-site-specific control), and 3 weeks later tested for spontaneous alloparental behavior and partner preference. Enhancing ERα in the MeA altered/reduced male prosocial behavior. Only one-third of MeA-ERα males, compared with all control males, were alloparental. MeA-ERα males also displayed a significant preference for a novel female. This is a critical finding because the manipulations of neuropeptides, oxytocin and vasopressin, can inhibit the formation of a partner preference, but do not lead to the formation of a preference for a novel female. The results support the hypothesis that low levels of ERα are necessary for high levels of male prosocial behavior, and provide the first direct evidence that site-specific ERα expression plays a critical role in the expression of male prosocial behavior.
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Because AVP/OT and the dopaminergic pathways they feed into are heavily influenced by sex steroids across the lifespan, their sexually dimorphic ontogeny and function may be particularly vulnerable to endocrine disruption.
“Because AVP/OT and the dopaminergic pathways they feed into are heavily influenced by sex steroids across the lifespan (50–59), it is highly plausible that their sexually dimorphic ontogeny and function may be particularly vulnerable to endocrine disruption.”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [56]
The Discussion (page unavailable) reports that neonatal castration altered adult male prairie voles’ response to vasopressin and that changing estrogen-receptor expression in adults altered social behavior. This supports a link between sex-steroid signaling and some vasopressin-related behavior, but the cited paper does not establish steroid effects on oxytocin or dopaminergic pathways across the lifespan. The endocrine-disruption vulnerability is the citing authors’ inference, not a finding attributed to this source. (LLM, conf=0.86)
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References 88 · Cited by 95
Research works printed but not linked: 24
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- Authors
- Cushing, B. S., Perry, A., Musatov, S., Ogawa, S., & Papademetriou, E.
- Affiliations
- University of Akron (US)
- Rockefeller University (US)
- University of Tsukuba (JP)
- University of Illinois Chicago (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-10-08
- Volume
- 28
- Issue
- 41
- Pages
- 10399-10403
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2586115
- OpenAlex
- W2156976362
- Cited by
- 95
- References
- 88
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 10 · 2017: 8 · 2016: 6 · 2015: 9 · 2014: 4 · 2013: 5 · 2012: 5
- FWCI
- 8.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH068278, R21MH068278, MH001992, K01MH001992)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- estrogen receptor alpha, medial amygdala, mate preferences, Microtus ochrogaster, masculinization, social behavior, oxytocin, vasopressin
- MeSH terms
- Amygdala, Animals, Behavior, Animal, Choice Behavior, Arvicolinae, Female, Humans, Inhibition, Psychological, Male, Sexual Behavior, Animal, Sex Characteristics, Social Behavior, Transfection, Up-Regulation, Estrogen Receptor alpha
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