Estrogen receptor 2b is the major determinant of sex-typical mating behavior and sexual preference in medaka
Yuji Nishiike, Daichi Miyazoe, Rie Togawa, Keiko Yokoyama, Kiyoshi Nakasone, Masayoshi Miyata, Yukiko Kikuchi, Yasuhiro Kamei, Takeshi Todo, Tomoko Ishikawa-Fujiwara, Kaoru Ohno, Takeshi Usami, Yoshitaka Nagahama, Kataaki Okubo*
Male and female animals typically display innate sex-specific mating behaviors, which, in vertebrates, are highly dependent on sex steroid signaling. While estradiol-17β (E2) signaling through estrogen receptor 2 (ESR2) serves to defeminize male mating behavior in rodents, the available evidence suggests that E2 signaling is not required in teleosts for either male or female mating behavior. Here, we report that female medaka deficient for Esr2b, a teleost ortholog of ESR2, are not receptive to males but rather court females, despite retaining normal ovarian function with an unaltered sex steroid milieu. Thus, contrary to both prevailing views in rodents and teleosts, E2/Esr2b signaling in the brain plays a decisive role in feminization and demasculinization of female mating behavior and sexual preference in medaka. Further behavioral testing showed that mutual antagonism between E2/Esr2b signaling and androgen receptor-mediated androgen signaling in adulthood induces and actively maintains sex-typical mating behaviors and preference. Our results also revealed that the female-biased sexual dimorphism in esr2b expression in the telencephalic and preoptic nuclei implicated in mating behavior can be reversed between males and females by altering the sex steroid milieu in adulthood, likely via mechanisms involving direct E2-induced transcriptional activation. In addition, Npba, a neuropeptide mediating female sexual receptivity, was found to act downstream of E2/Esr2b signaling in these brain nuclei. Collectively, these functional and regulatory mechanisms of E2/Esr2b signaling presumably underpin the neural mechanism for induction, maintenance, and reversal of sex-typical mating behaviors and sexual preference in teleosts, at least in medaka.
- : Current Biology
- : 10.1016/j.cub.2021.01.089
- : https://www.cell.com/current-biology/fulltext/S0960-9822(21)00154-8