Estrogen masculinizes neural pathways and sex-specific behaviors - PMC
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Cell<br>. Author manuscript; available in PMC: 2010 Oct 2.
Published in final edited form as: Cell. 2009 Oct 2;139(1):61–72. doi: 10.1016/j.cell.2009.07.036
Estrogen masculinizes neural pathways and sex-specific behaviors
Melody V Wu<br>Melody V Wu
1 Program in Neuroscience, University of California, San Francisco, MC 2722, San Francisco, CA 94158
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1, Devanand S Manoli<br>Devanand S Manoli
4 Department of Psychiatry, University of California, San Francisco, MC 2722, San Francisco, CA 94158
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4, Eleanor J Fraser<br>Eleanor J Fraser
2 Program in Genetics, University of California, San Francisco, MC 2722, San Francisco, CA 94158
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2, Jennifer K Coats<br>Jennifer K Coats
1 Program in Neuroscience, University of California, San Francisco, MC 2722, San Francisco, CA 94158
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1, Jessica Tollkuhn<br>Jessica Tollkuhn
3 Department of Anatomy, University of California, San Francisco, MC 2722, San Francisco, CA 94158
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3, Shin-Ichiro Honda<br>Shin-Ichiro Honda
5 School of Medicine, Fujita Health University, Toyoake, Aichi Japan
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5, Nobuhiro Harada<br>Nobuhiro Harada
5 School of Medicine, Fujita Health University, Toyoake, Aichi Japan
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5, Nirao M Shah<br>Nirao M Shah
1 Program in Neuroscience, University of California, San Francisco, MC 2722, San Francisco, CA 94158
2 Program in Genetics, University of California, San Francisco, MC 2722, San Francisco, CA 94158
3 Department of Anatomy, University of California, San Francisco, MC 2722, San Francisco, CA 94158
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1,2,3,*
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1 Program in Neuroscience, University of California, San Francisco, MC 2722, San Francisco, CA 94158
2 Program in Genetics, University of California, San Francisco, MC 2722, San Francisco, CA 94158
3 Department of Anatomy, University of California, San Francisco, MC 2722, San Francisco, CA 94158
4 Department of Psychiatry, University of California, San Francisco, MC 2722, San Francisco, CA 94158
5 School of Medicine, Fujita Health University, Toyoake, Aichi Japan
Corresponding author. nms@ucsf.edu; Tel: (415)514-4381; Fax: (415)476-1974
PMC Copyright notice
PMCID: PMC2851224 NIHMSID: NIHMS136250 PMID: 19804754
The publisher's version of this article is available at Cell
See commentary "Sex on the brain." on page 19.
SUMMARY
Male behaviors require both testosterone and estrogen. Circulating testosterone activates the androgen receptor (AR) and is also converted into estrogen in the brain via aromatase. This conversion is the primary source of estrogen to the male brain. It is unclear whether testosterone and estrogen signaling interact to masculinize neural circuits. Using a genetic approach, we show extensive sexual dimorphism in the number and projections of aromatase expressing neurons. The masculinization of these cells is independent of AR but can be induced by either testosterone or estrogen, indicating a role for aromatase in sexual differentiation of these neurons. We provide evidence suggesting that aromatase is also important in activating male aggression and urine marking as these behaviors can be elicited by testosterone in males mutant for AR. Taken together with additional findings, our results suggest that aromatization of testosterone into estrogen is important for the development and activation of neural circuits that control male territorial behaviors.
INTRODUCTION
All sexually reproducing species exhibit gender dimorphisms in behavior. Such sex differences can be observed in various displays, including in mating, aggression, territorial marking, and parental care. Behavioral dimorphisms can be observed in socially naive animals suggesting that sexual differentiation of the underlying neural circuits is tightly controlled by internal physiological regulators. In vertebrates, gonadal steroid hormones play a central role in the development and function of these neural circuits (Arnold et al., 2003; Goy and McEwen, 1980; Morris et al., 2004). Both testosterone and estrogen are required for male...