Neuroestrogens facilitate male-typical behaviors by potentiating androgen receptor signaling in medaka

Nishiike, Y.; Maki, S.; Miyazoe, D.; Nakasone, K.; Kamei, Y.; Todo, T.; Ishikawa-Fujiwara, T.; Ohno, K.; Usami, T.; Nagahama, Y.; Okubo, K.

doi:10.1101/2024.02.13.580203

bioRxiv · 10.1101/2024.02.13.580203

Neuroestrogens facilitate male-typical behaviors by potentiating androgen receptor signaling in medaka

Nishiike, Y.·Maki, S.·Miyazoe, D.·Nakasone, K.·Kamei, Y.·Todo, T.·Ishikawa-Fujiwara, T.·Ohno, K.·Usami, T.·Nagahama, Y.·Okubo, K.

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Abstract

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. Taken together, these findings reveal a previously unappreciated mode of action of brain-derived estrogens in shaping male-typical behaviors.

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Nishiike, Y., Maki, S., Miyazoe, D., Nakasone, K., Kamei, Y., Todo, T., Ishikawa-Fujiwara, T., Ohno, K., Usami, T., Nagahama, Y., Okubo, K.. 2024-02-16. Neuroestrogens facilitate male-typical behaviors by potentiating androgen receptor signaling in medaka. https://doi.org/10.1101/2024.02.13.580203

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