Boosting effect of testosterone on GDNF expression in Sertoli cell line (TM4); comparison between TM3 cells-produced and exogenous testosterone

Gene. 2022 Feb 20:812:146112. doi: 10.1016/j.gene.2021.146112. Epub 2021 Dec 9.

Abstract

The Glial cell-derived neurotrophic factor (Gdnf) and testosterone induce the spermatogonial stem cells (SSCs) self-renewal and spermatogenesis, respectively. In present study the stimulating role of testosterone on Sertoli cells to produce Gdnf, and the possible effect of Gdnf on Gfrα1 and c-RET expressions were investigated. The TM4 cells (line Sertoli cells) were co-cultured with [0.1, 0.2 and 0.4 (ng/ml)] of exogenous and TM3 (line Leydig cells)-produced testosterones, and consequently the TM4-produced Gdnf concentration was evaluated. Next, the SSCs were co-cultured with the TM-4 derived media (endogenous Gdnf) and exogenous Gdnf [0.1, 0.2, and 0.4 ng/ml)]. The 0.1 and 0.2 ng/ml endogenous and 3 concentrations of exogenous testosterone up-regulated the Gdnf expression versus non-treated Sertoli cells. The TM4-produced and exogenous Gdnfs, in all concentrations, up-regulated the receptors expression. In conclusion, the testosterone, solely, stimulates the Gdnf synthesis and the Gdnf, individually, amplifies its receptor's expression at mRNA and protein levels.

Keywords: Gdnf; Gfrα1; Self-renewal; Spermatogonial stem cell; Testosterone; c-RET.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Coculture Techniques
  • Gene Expression Regulation / drug effects
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism*
  • Leydig Cells / cytology*
  • Leydig Cells / metabolism
  • Male
  • Mice
  • Sertoli Cells / cytology*
  • Sertoli Cells / drug effects
  • Sertoli Cells / metabolism
  • Testosterone / metabolism*
  • Testosterone / pharmacology
  • Up-Regulation

Substances

  • Gdnf protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor
  • Testosterone