The Androgen Receptor Governs the Execution, but Not Programming, of Male Sexual and Territorial Behaviors
Open accessAbstract
Testosterone and estrogen are essential for male behaviors in vertebrates. How these two signaling pathways interact to control masculinization of the brain and behavior remains to be established. Circulating testosterone activates the androgen receptor (AR) and also serves as the source of estrogen in the brain. We have used a genetic strategy to delete AR specifically in the mouse nervous system. This approach permits us to determine the function of AR in sexually dimorphic behaviors in males while maintaining circulating testosterone levels within the normal range. We find that AR mutant males exhibit masculine sexual and territorial displays, but they have striking deficits in specific components of these behaviors. Taken together with the surprisingly limited expression of AR in the developing brain, our findings indicate that testosterone acts as a precursor to estrogen to masculinize the brain and behavior, and signals via AR to control the levels of male behavioral displays.
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Male rodents lacking gonads, androgen receptors or estrogen receptors display substantially decreased aggression and sexual behaviours.
“Male rodents lacking gonads, androgen receptors or estrogen receptors display substantially decreased aggression and sexual behaviours [8–11]”
From Effects of sex and gonadectomy on social investigation and social recognition in mice (2015) · cites this paper as [9]
The Discussion reports substantial deficits in mating and territorial behaviour in male mice lacking neural androgen receptors, and the Introduction reports loss of male sexual and aggressive behaviours in mice lacking both estrogen receptors. These passages concern mice rather than rodents generally. Our copy does not establish the claimed behavioural decrease in males lacking gonads. (LLM, conf=0.85)
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“Both testosterone and estrogen, however, appear critical during development and adult life in males for the display of dimorphic behaviors such as intermale aggression (Bakker et al., 2006; Finney and Erpino, 1976; Motelica-Heino et al., 1993; Wu et al., 2009).”
Brain masculinization requires androgen receptor function
Sato, T., Matsumoto, T., Kawano, H., Watanabe, T., Uematsu, Y., Sekine, K., Fukuda, T., Aihara, K.-I., Krust, A., Yamada, T., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0305303101 · Cited by 303 · see citing works
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“Mice exhibit a large array of behavioral dimorphisms beyond sexual and territorial displays, and it will be important in future studies to determine whether AR function in the nervous system is essential for the appropriate display of such behaviors (Zuloaga et al., 2008a, 2008b).”
Distribution of estrogen receptor alpha and beta immunoreactive profiles in the postnatal rat brain
Pérez, S. E., Chen, E.-Y., & Mufson, E. J. (2003) · Developmental Brain Research · doi:10.1016/s0165-3806(03)00223-2 · Cited by 228 · see citing works
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- Authors
- Juntti, S. A., Tollkuhn, J., Wu, M. V., Fraser, E. J., Soderborg, T., Tan, S., Honda, S.-I., Harada, N., & Shah, N. M.
- Affiliations
- University of California, San Francisco (US)
- Fujita Health University (JP)
- Corresponding author
- Shah, Nirao M.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 66
- Issue
- 2
- Pages
- 260-272
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC2923659
- OpenAlex
- W2132769858
- Cited by
- 254
- References
- 10
- Citations by year
- 2026: 12 · 2025: 11 · 2024: 23 · 2023: 19 · 2022: 16 · 2021: 18 · 2020: 12 · 2019: 14 · 2018: 15 · 2017: 21 · 2016: 13 · 2015: 16 · 2014: 11 · 2013: 14 · 2012: 15
- FWCI
- 6.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1203 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- National Science Foundation
- National Institutes of Health (DP1OD006425)
- University of California, San Francisco
- Japan Society for the Promotion of Science (22591019)
- National Institute of Neurological Disorders and Stroke (R01NS049488)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (F32HD0612472)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Keywords
- androgen receptor, testosterone, estrogen, sexual behavior, territoriality, sexually dimorphic behavior, male behavior, neuroendocrine signaling
- MeSH terms
- Animals, Brain, Estrogens, Male, Mice, Transgenic, Neurons, Receptors, Androgen, Sexual Behavior, Animal, Territoriality, Testosterone, Mice
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