Male-specific behavior requires female hormones — Significance of massive production in male brains elucidated

A research group led by Professor Kataaki Okubo and Mr. Yuji Nishiike (a graduate student at the time of the research) from the Graduate School of Agricultural and Life Sciences at the University of Tokyo, in collaboration with the National Institute for Basic Biology and the University of Osaka, announced that they have clarified the significance of massive estrogen production in male brains. The research revealed that estrogen produced in the male brain enhances brain sensitivity to androgens, thereby promoting male-specific behaviors. Male medaka fish that lost the ability to produce estrogen in their brains showed reduced courtship toward females and stopped attacking other males. These results were published in eLife on January 13.

Female hormones (estrogens) are important for females and mainly produced in the ovaries, playing a crucial role in egg development, but the reason why massive amounts of female hormones are also produced in male brains had long remained a mystery. In vertebrates, androgens are considered important for male-specific behaviors. In most species, it was believed that estrogens were not necessary for male-specific behaviors.

Therefore, the researchers investigated the behavior of medaka offspring that inherited a genetic mutation preventing estrogen production in the brain induced by the TILLING method, which artificially induces mutations.

The results showed that courtship toward females and aggression toward other males were significantly reduced. Furthermore, when these males were administered estrogen, courtship toward females recovered to the same level as normal males.

Additionally, the researchers found that estrogen produced in the brain has the effect of increasing the amount of androgen receptors (which, when activated, generate various male-specific behaviors and characteristics) in brain regions involved in social behaviors. Through this effect, the synthesis of brain hormones involved in courtship toward females and aggression toward males increased. The synthesis of these brain hormones was significantly reduced in males that could no longer produce estrogen in the brain.

These findings revealed that estrogen produced in the male brain triggers male-specific behaviors by enhancing brain sensitivity to androgens.

Okubo commented: "We are pleased to have provided an answer to the long-standing question of why massive amounts of estrogen, generally considered important for females, are also produced in male brains. In order for androgens to act on the male brain and trigger male-specific courtship and aggressive behaviors, estrogen must first act on the brain to prepare the groundwork for androgens to take effect. We ourselves were surprised by this unexpected mechanism."

Journal Information
Publication: eLife
Title: Brain-derived estrogens facilitate male-typical behaviors by potentiating androgen receptor signaling in medaka
DOI: 10.7554/eLife.97106.4