Brain masculinization requires androgen receptor function.

  title={Brain masculinization requires androgen receptor function.},
  author={Takashi R. Sato and Takahiro Matsumoto and Hirotaka Kawano and Tomoyuki Watanabe and Yoshikatsu Uematsu and Keisuke Sekine and Toru Fukuda and Ken-ichi Aihara and Andrée Krust and Takashi Yamada and Yuko Nakamichi and Yoko Yamamoto and Takashi Nakamura and Kimihiro Yoshimura and Tatsuya Yoshizawa and Daniel Metzger and Pierre Chambon and Shigeaki Kato},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  volume={101 6},
Testicular testosterone produced during a critical perinatal period is thought to masculinize and defeminize the male brain from the inherent feminization program and induce male-typical behaviors in the adult. These actions of testosterone appear to be exerted not through its androgenic activity, but rather through its conversion by brain aromatase into estrogen, with the consequent activation of estrogen receptor (ER)-mediated signaling. Thus, the role of androgen receptor (AR) in perinatal… 

Figures from this paper

Conditional Inactivation of Androgen Receptor Gene in the Nervous System: Effects on Male Behavioral and Neuroendocrine Responses
Findings show that central AR is required in T-induced regulation of male-typical behaviors and gonadotrope and somatotropic axes and offers a unique opportunity in the understanding of AR's role in cerebral functions of T.
Genetic impact of both sex hormones in male-typical behaviors.
The cooperative role of sex hormones signaling in brain sex differences underlying the expression of male-typical behaviors is described here and essential role of AR for normal folliculogenesis suggests that androgen/AR signaling is also physiologically important in females.
Role for estradiol in female-typical brain and behavioral sexual differentiation
Estrogen Masculinizes Neural Pathways and Sex-Specific Behaviors
Nonneural Androgen Receptors Affect Sexual Differentiation of Brain and Behavior.
The results suggest novel roles for nonneural AR in sexual differentiation of mice, and indicate that excess AR can lead to a paradoxical reduction of male-typical behavior.
Brain feminization requires active repression of masculinization via DNA methylation
RNA sequencing revealed gene and isoform variants modulated by methylation that may underlie the divergent reproductive behaviors of males versus females and show that brain feminization is maintained by the active suppression of masculinization via DNA methylation.


Behavioral effects of estrogen receptor gene disruption in male mice.
It is indicated that ER gene expression during development plays a major role in the organization of male-typical aggressive and emotional behaviors in addition to simple sexual behaviors.
Alteration in Sex-Specific Behaviors in Male Mice Lacking the Aromatase Gene
The results support the brain aromatization hypothesis and indicate that aromatase gene expression is a critical step not only for motivational and consummatory aspects of male sexual behavior, but also for aggressive and parental behaviors in male mice.
Survival of reproductive behaviors in estrogen receptor β gene-deficient (βERKO) male and female mice
Not only did βERKO males exhibit normal male-typical aggressive behavior, including offensive attacks, but they also showed higher levels of aggression than wild-type mice under certain conditions of social experience, revealing a significant interaction between genotype and social experience with respect to aggressive behavior.
Abolition of male sexual behaviors in mice lacking estrogen receptors alpha and beta (alpha beta ERKO).
  • S. Ogawa, A. E. Chester, D. Pfaff
  • Biology, Psychology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2000
Either one of the ERs is sufficient for the expression of simple mounting in male mice, indicating a redundancy in function, whereas Offensive attacks, on the other hand, depend specifically on the ER-alpha gene.
Generation and characterization of androgen receptor knockout (ARKO) mice: An in vivo model for the study of androgen functions in selective tissues
The cre-lox ARKO mouse provides a much-needed in vivo animal model to study androgen functions in the selective androgen target tissues in female or male mice, suggesting potential defects in female fertility and/or ovulation.
Androgen receptor defects : Historical, clinical, and molecular perspectives
AIS is an archetypal example of a hormone resistance disorder; however, due to defective androgen receptor (AR1) function, there is loss of target organ response to the hormone, and the effects of androgens are reduced or absent.