Neuroestrogens Critically Regulate Male-Typical Behaviors in Medaka Fish by Enhancing Androgen Receptor Signaling

Temel Kavramlar

Neuroestrogens, brain-derived estrogens, are essential for the development of male-typical mating and aggressive behaviors in medaka fish by potentiating androgen receptor signaling in behaviorally relevant brain regions.

Özet

The study investigated the role of neuroestrogens in regulating male-typical behaviors in medaka fish, a teleost species. Key findings:

Male medaka lacking the brain-specific aromatase enzyme Cyp19a1b, which is responsible for local estrogen synthesis, exhibited severely impaired mating and aggressive behaviors despite elevated brain androgen levels.

These behavioral deficits could be rescued by estrogen administration, indicating that neuroestrogens are pivotal for male-typical behaviors in medaka.

Neuroestrogens facilitate male behaviors by directly stimulating the transcription of androgen receptor (AR) subtypes Ara and Arb in behaviorally relevant brain regions, primarily through the estrogen receptor (ESR) subtypes Esr2a and Esr1, respectively.

Cyp19a1b-deficient females showed reduced sexual receptivity to males and instead exhibited male-typical courtship behavior towards other females, demonstrating that neuroestrogens also play a critical role in establishing sex-typical behaviors in both sexes.

The findings challenge the prevailing view that neuroestrogens have little effect on male behaviors in species where testicular androgens directly elicit these behaviors, and reveal a previously unappreciated mechanism of neuroestrogen action that may be evolutionarily conserved across vertebrates.

İstatistikler

"Brain estradiol-17β (E2) in both male and female homozygous mutants (cyp19a1b−/−) was significantly reduced to 16% and 50%, respectively, of the levels in their wild-type (cyp19a1b+/+) siblings."
"Brain testosterone levels in cyp19a1b−/− males increased 2.2-fold relative to wild-type siblings."
"Brain 11-ketotestosterone (11KT) levels in cyp19a1b−/− males and females increased 6.2- and 1.9-fold, respectively, versus wild-type siblings."

Alıntılar

"Contrary to our expectation, however, cyp19a1b−/− males showed significantly longer latencies to initiate wrappings (P = 0.0033 versus cyp19a1b+/+, P = 0.0195 versus cyp19a1b+/−) and to spawn (P = 0.0051 versus cyp19a1b+/+, P = 0.0195 versus cyp19a1b+/−), suggesting that they are less motivated to mate."
"E2 treatment, while having no effect in cyp19a1b+/+ males, significantly shortened the latency to (P = 0.0005) and increased the number of (P = 0.0006) courtship displays in cyp19a1b−/− males, demonstrating that reduced E2 in the brain was the primary cause of the mating defects."
"Expression of ara was significantly lower in cyp19a1b−/− males than in cyp19a1b+/+ males in several preoptic and hypothalamic nuclei that are activated upon mating and/or attack in males."

Önemli Bilgiler Şuradan Elde Edildi

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

by Nishiike,Y.,... : www.biorxiv.org 02-16-2024

https://www.biorxiv.org/content/10.1101/2024.02.13.580203v1

Daha Derin Sorular

How do neuroestrogens interact with other neurotransmitter or neuromodulator systems to influence the neural circuits underlying sex-typical behaviors

Neuroestrogens interact with other neurotransmitter or neuromodulator systems to influence the neural circuits underlying sex-typical behaviors through complex mechanisms. In the context of the study on medaka fish, neuroestrogens were shown to potentiate androgen receptor (AR) signaling in behaviorally relevant brain regions by directly stimulating AR transcription. This interaction between neuroestrogens and ARs is crucial for the expression of male-typical mating and aggressive behaviors. Additionally, neuroestrogens may modulate the activity of other neurotransmitter systems, such as vasotocin and galanin, which have been implicated in male behaviors in various vertebrates. The interplay between neuroestrogens and these neurotransmitter systems likely fine-tunes the neural circuits responsible for sex-typical behaviors.

What are the evolutionary pressures that have led to the divergent roles of neuroestrogens in regulating male behaviors across different vertebrate lineages

The divergent roles of neuroestrogens in regulating male behaviors across different vertebrate lineages can be attributed to evolutionary pressures shaping the reproductive strategies and social behaviors of each species. In some species, such as rodents, neuroestrogens are essential for the development of male-typical behaviors through the aromatization of androgens in the brain. This mechanism may have evolved to optimize reproductive success and social interactions in these species. On the other hand, in teleost fish like medaka, where androgens directly facilitate male behaviors without aromatization, neuroestrogens play a modulatory role by potentiating androgen/AR signaling. The evolutionary divergence in the roles of neuroestrogens reflects the diverse adaptations of vertebrates to their ecological niches and social structures.

Could the mechanisms by which neuroestrogens regulate sex-typical behaviors be leveraged to develop novel therapeutic interventions for disorders of sexual differentiation or gender identity

The mechanisms by which neuroestrogens regulate sex-typical behaviors offer potential avenues for developing novel therapeutic interventions for disorders of sexual differentiation or gender identity. Understanding how neuroestrogens modulate AR signaling and influence the neural circuits underlying male and female behaviors could provide insights into the pathophysiology of such disorders. By targeting the neuroestrogen-AR interaction, it may be possible to modulate the expression of genes involved in sexual differentiation and gender identity. This could lead to the development of targeted therapies that aim to restore or modulate the neuroendocrine pathways involved in sex-typical behaviors, offering new treatment options for individuals with disorders related to sexual development and gender identity.