Androgen induced cellular proliferation, neurogenesis, and generation of GnRH3 neurons in the brain of mature female Mozambique tilapia

Abstract

The neuroplastic mechanisms in the fish brain that underlie sex reversal remain unknown. Gonadotropin-releasing hormone 3 (GnRH3) neurons control male reproductive behaviours in Mozambique tilapia and show sexual dimorphism, with males having a greater number of GnRH3 neurons. Treatment with androgens such as 11-ketotestosterone (KT), but not 17β-estradiol, increases the number of GnRH3 neurons in mature females to a level similar to that observed in mature males. Compared with oestrogen, the effect of androgen on neurogenesis remains less clear. The present study examined the effects of 11-KT, a non-aromatizable androgen, on cellular proliferation, neurogenesis, generation of GnRH3 neurons and expression of cell cycle-related genes in mature females. The number of proliferating cell nuclear antigen-positive cells was increased by 11-KT. Simultaneous injection of bromodeoxyuridine and 11-KT significantly increased the number of newly-generated (newly-proliferated) neurons, but did not affect radial glial cells, and also resulted in newly-generated GnRH3 neurons. Transcriptome analysis showed that 11-KT modulates the expression of genes related to the cell cycle process. These findings suggest that tilapia could serve as a good animal model to elucidate the effects of androgen on adult neurogenesis and the mechanisms for sex reversal in the fish brain.

Gonadotropin Releasing Hormone (GnRH) Triggers Neurogenesis in the Hypothalamus of Adult Zebrafish

“…These results contrast with studies in the other teleosts (Tilapia), where testosterone treatment increased proliferation in the periventricular regions of the brain. However, like the findings presented here, the BrdU labeling was not found in radial glia cells [59]. Although we found a slight increase in proliferation with testosterone treatment, consistent with our previous study performed in hypothalamic neural progenitor cells in vitro, the effect was minimal with a small, but significant, increase in neurons in cultured hypothalamic progenitor cells [59].…”

Direct and Indirect Effects of Sex Steroids on Gonadotrope Cell Plasticity in the Teleost Fish Pituitary

“…In Mozambique tilapia, Gnrh3 neurons are more numerous in males, and treatment with 11-KT or methyltestosterone (MT, a potent synthetic androgen), but not E2, increased the number of Gnrh3 neurons in females to a level similar to that in males, and modified the fish behavior (262). Recently, the same group showed that this phenomenon was due to proliferation by identifying newly formed Gnrh3 neurons after androgen treatment (263). In larval zebrafish, treatment with the synthetic estrogen 17a-ethinylestradiol (EE2) increased the numbers of forebrain Gnrh3 cells (264).…”

Single-Cell Gene Profiling Reveals Social Status-Dependent Modulation of Nuclear Hormone Receptors in GnRH Neurons in a Male Cichlid Fish

“…However, the differential expression levels of ER types in GnRH2 and GnRH3 neurons could indicate the presence of estrogenic feedback mechanism on nonphysiotropic GnRH types. In zebrafish, estrogen has been demonstrated to contribute to the regulation of neuronal development of GnRH3 neurons [68], although estrogen had no effect on the number of GnRH3 neurons in male tilapia [69]. However, there are still a couple of limitations to associating gene expression profiles within GnRH neurons with social status.…”