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

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 receptor...

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Bibliographic Details
Published in:Hormones and behavior 2008-05, Vol.53 (5), p.613-626
Main Authors: Zuloaga, Damian G., Puts, David A., Jordan, Cynthia L., Breedlove, S. Marc
Format: Article
Language:English
Subjects:
Aggression
Animal behavior
Animals
Anxiety
Bed nucleus
Behavior, Animal - physiology
Brain
Brain - anatomy & histology
Brain - growth & development
Brain - physiology
Complete androgen insensitivity syndrome — CAIS
Female
Feminization - genetics
Humans
Male
Masculinity
Medial amygdala
Mutation - physiology
Receptors, Androgen - physiology
Rodents
SDN-POA
Sex Differentiation - physiology
Sexual behavior
Social Behavior
Spatial memory
Testosterone
Vasopressin
VMH
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Summary: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.
ISSN:0018-506X
1095-6867
DOI:10.1016/j.yhbeh.2008.01.013