Biology subjects

Nishiike, Y.

Publications and source records attributed to Nishiike, Y..

3 recordsLinked to original sources

bioRxiv2024

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

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.

physiology↗

bioRxiv2024

The decision of male medaka to mate or fight depends on two complementary androgen signaling pathways

Adult male animals typically court and attempt to mate with females, while attacking other males. Emerging evidence from mice indicates that neurons expressing the estrogen receptor ESR1 in behaviorally relevant brain regions play a central role in mediating these mutually exclusive behavioral responses to conspecifics. However, the findings in mice are unlikely to apply to most other vertebrates, where androgens -- rather than estrogens -- have been implicated in male behaviors. Here we report that male medaka (Oryzias latipes) lacking one of the two androgen receptor subtypes (Ara) are less aggressive toward other males and instead actively court them, while those lacking the other subtype (Arb) are less motivated to mate with females and conversely attack them. These findings indicate that, in male medaka, the Ara- and Arb-mediated androgen signaling pathways facilitate appropriate behavioral responses, while simultaneously suppressing inappropriate responses, to males and females, respectively. Notably, males lacking either receptor retain the ability to discriminate the sex of conspecifics, suggesting a defect in the subsequent decision-making process to mate or fight. We further show that Ara and Arb are expressed in intermingled but largely distinct populations of neurons, and stimulate the expression of different behaviorally relevant genes including galanin and vasotocin, respectively. Collectively, our results demonstrate that male teleosts make adaptive decisions to mate or fight as a result of the activation of one of two complementary androgen signaling pathways, depending on the sex of the conspecific that they encounter.

physiology↗

bioRxiv2023

Cholecystokinin is the follicle-stimulating hormone (FSH)-releasing hormone

In vertebrates, folliculogenesis and ovulation are regulated by two distinct pituitary gonadotropins: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Today, there is an intriguing consensus that a single hypothalamic neurohormone, gonadotropin-releasing hormone (GnRH), regulates the secretion of both FSH and LH, although the required timing and functions of FSH and LH are different. However, recent studies in vertebrates other than mammals indicate that the effect of GnRH on FSH is too weak to explain its regulation. Therefore, to challenge this "solo GnRH model," we aimed to identify the other gonadotropin regulator, FSH-releasing hormone (FSH-RH), in vertebrates. Here, by using the model teleost medaka, we successfully identified cholecystokinin as the FSH-RH. Our histological and in vitro analyses demonstrated that hypothalamic cholecystokinin-expressing neurons directly affect FSH cells through the cholecystokinin receptor, Cckbr1, thereby increasing the expression and release of FSH. Remarkably, the knockout of cholecystokinin ligand or cckbr1 minimized FSH expression and resulted in a complete failure of folliculogenesis. Our results challenge the longstanding consensus of the solo GnRH model in all vertebrates; instead, we propose the existence of a "dual GnRH model" group in vertebrates that utilizes both FSH-RH and LH-RH. The discovery of the FSH-RH in vertebrates opens not only a new era in neuroendocrinology but also possible applications involving vertebrate reproduction.

neuroscience↗