Genetic impact of both sex hormones in male-typical behaviors

Androgens have a critical role in a wide range of biological processes. These include spermatogenesis, development of reproductive organs, and brain function. Most actions of androgens are mediated by the nuclear androgen receptor (AR), which acts as a ligand-inducible transcription factor. To elucidate physiological significance of AR in target tissues, we succeeded in disrupting the AR on the X chromosome using a Cre-loxP system. Male AR-null mutant (ARKO) mice exhibit abnormalities typical of testicular feminization mutants (Tfm), including female external genitalia with atrophic testis [1]. They also develop late-onset obesity [2] with glucocorticoid overproduction [3] and impaired bone growth coupled with high bone turnover [4]. Moreover, essential role of AR for normal folliculogenesis suggests that androgen/AR signaling is also physiologically important in females [5]. On the other hand, the physiological role of AR-mediated androgen signaling in brain masculinization has not been established. We describe here the cooperative role of sex hormones signaling in brain sex differences underlying the expression of male-typical behaviors.