Mechanistic target of rapamycin (mTOR) implicated in plasticity of the reproductive axis during social status transitions

• Published in: General and comparative endocrinology 2019-10, Vol.282, p.113209-113209, Article 113209
• Main Authors: Maruska, Karen P., Sohn, Young Chang, Fernald, Russell D.
• Format: Article
• Language: English
• Subjects: Animals; Brain; Brain - drug effects; Brain - metabolism; Cichlid; Cichlids - genetics; Cichlids - physiology; Gene Expression Regulation - drug effects; GnRH1; Gonadotropin-Releasing Hormone - metabolism; Male; Neuronal Plasticity - drug effects; Neurons - drug effects; Neurons - metabolism; Phosphorylation - drug effects; Pituitary; Pituitary Gland - drug effects; Pituitary Gland - metabolism; Reproduction - drug effects; Reproduction - physiology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sexual Maturation - drug effects; Sirolimus - pharmacology; Social Dominance; Teleost; Testis; Testis - drug effects; Testis - metabolism; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism
• ISSN: 0016-6480; 1095-6840
• DOI: 10.1016/j.ygcen.2019.113209

•mtor is localized to the brain, pituitary, and testis of a cichlid fish.•mtor plays a role in GnRH1 neuron plasticity.•mtor expression changes during a rise in male social rank.•Inhibition of mtor with rapamycin impacts the brain, pituitary, and testis.•mtor regulation of the reproductive axis is conserved to fishes. The highly conserved brain-pituitary-gonadal (BPG) axis controls reproduction in all vertebrates, so analyzing the regulation of this signaling cascade is important for understanding reproductive competence. The protein kinase mechanistic target of rapamycin (mTOR) functions as a conserved regulator of cellular growth and metabolism in all eukaryotes, and also regulates the reproductive axis in mammals. However, whether mTOR might also regulate the BPG axis in non-mammalian vertebrates remains unexplored. We used complementary experimental approaches in an African cichlid fish, Astatotilapia burtoni, to demonstrate that mTOR is involved in regulation of the brain, pituitary, and testes when males rise in rank to social dominance. mTOR or downstream components of its signaling pathway (p-p70S6K) were detected in gonadotropin-releasing hormone (GnRH1) neurons, the pituitary, and testes. Transcript levels of mtor in the pituitary and testes also varied when reproductively-suppressed subordinate males rose in social rank to become dominant reproductively-active males, a transition similar to puberty in mammals. Intracerebroventricular injection of the mTORC1 inhibitor, rapamycin, revealed a role for mTOR in the socially-induced hypertrophy of GnRH1 neurons. Rapamycin treatment also had effects at the pituitary and testes, suggesting involvement of the mTORC1 complex at multiple levels of the reproductive axis. Thus, we show that mTOR regulation of BPG function is conserved to fishes, likely playing important roles in regulating reproduction and fertility across all male vertebrates.