Estrogen/Esr2b signaling‐dependent, female‐biased expression of a neuropeptide Y gene in the medaka brain

Abstract A recent study showed that female medaka lacking the estrogen receptor gene esr2b are unreceptive to male courtship and instead court other females. In this study, we investigated the brain transcriptome of esr2b ‐deficient females to explore the underlying mechanisms of this behavioral phenotype, and identified npyb , one of the two neuropeptide Y (NPY) genes in teleosts, as substantially downregulated. Follow‐up analyses revealed that npyb is expressed in a markedly female‐biased manner, dependent on estrogen/Esr2b signaling, in a ventral telencephalic nucleus implicated in mating behavior. These findings led us to hypothesize that npyb may mediate the phenotypic consequence of esr2b deficiency. To test this, we generated npyb ‐deficient medaka and assessed their mating behavior; however, no notable abnormalities were observed. Given that npya , the other NPY gene in teleosts, is also expressed in the same brain nucleus, we considered the possibility that npya compensates for the loss of npyb function. Nevertheless, even medaka lacking both npya and npyb showed no discernible deficits in mating behavior. While the precise physiological roles of NPY in medaka remain elusive, our findings establish npyb as a downstream target of estrogen/Esr2b signaling and demonstrate its female‐biased expression in a behaviorally relevant brain region.