Brain-derived estrogens facilitate male-typical behaviors by potentiating androgen receptor signaling in medaka

This is the authors' abstract. We don't add key points for this paper.

In rodents, estrogens aromatized from androgens in the brain are essential for the development of male-typical behaviors. In many other vertebrates including humans and teleost fish, however, androgens facilitate these behaviors directly via the androgen receptor without aromatization into estrogens. Here we report that mutagenesis-derived male medaka fish lacking Cyp19a1b (a subtype of aromatase predominantly expressed in the brain) exhibit severely impaired male-typical mating and aggression, despite elevated brain androgen levels. These phenotypes can be rescued by estrogen administration, indicating that brain-derived estrogens are pivotal for male-typical behaviors even in teleosts. Our results further suggest that these estrogens facilitate male-typical behaviors by potentiating androgen action in the brain via the direct stimulation of androgen receptor transcription, thereby revealing a previously unappreciated mode of action of brain-derived estrogens. We additionally show that female fish lacking Cyp19a1b are less receptive to male courtship and conversely court other females, highlighting the significance of brain-derived estrogens in establishing sex-typical behaviors in both sexes.