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

Sci Rep. 2018 Nov 15;8(1):16855. doi: 10.1038/s41598-018-35303-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / pharmacology*
  • Animals
  • Brain / cytology*
  • Brain / metabolism*
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Proliferation / drug effects
  • Cerebral Ventricles / cytology
  • Female
  • Gene Expression Regulation / drug effects
  • Glial Fibrillary Acidic Protein / metabolism
  • Gonadotropin-Releasing Hormone / metabolism*
  • Image Processing, Computer-Assisted
  • Neurogenesis / drug effects*
  • Neuroglia / cytology
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Testosterone / analogs & derivatives
  • Testosterone / pharmacology
  • Tilapia / metabolism*

Substances

  • Androgens
  • Glial Fibrillary Acidic Protein
  • Proliferating Cell Nuclear Antigen
  • Gonadotropin-Releasing Hormone
  • Testosterone
  • 11-ketotestosterone