Increment of murine spermatogonial cell number by gonadotropin-releasing hormone analogue is independent of stem cell factor c-kit signal

Biol Reprod. 2003 Jun;68(6):2304-13. doi: 10.1095/biolreprod.102.013276. Epub 2003 Feb 5.


Recent studies have demonstrated that GnRH-analogues can stimulate regeneration of spermatogenesis of rats when administered after testicular damages. Although the mechanism of this phenomenon has not been elucidated yet, stem cell factor (SCF) produced by Sertoli cells was proposed to mediate the effects of GnRH-analogues on spermatogonial proliferation and/or survival. In the present study, we quantitatively evaluated the proliferation of spermatogonia and addressed whether SCF mediates the effect of GnRH-analogue on spermatogonial proliferation, using a novel approach combining spermatogonial transplantation and laser confocal microscopic observation. In the first experiment, using wild-type mice as recipients for spermatogonial transplantation, the number of donor spermatogonia per 100 Sertoli cells in each spermatogenic colony was significantly higher in the experimental group of mice treated with leuprorelin, a GnRH-agonist, than that of the control group at 4 and 5 wk after transplantation. In the second experiment, Steel/Steeldickie (Sl/Sld) mutant mice, which lack expression of membrane bound form SCF, were used as recipients. As seen in the first experiment, the number of undifferentiated spermatogonia was significantly higher in leuprorelin-treated than in the control group. Since undifferentiated spermatogonia do not express the receptor of SCF, the present study clearly demonstrates that neither membrane-bound nor secreted forms of SCF are involved in the mechanism of GnRH-analogue's effect on spermatogonial proliferation and/or survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Germ Cells / drug effects
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Gonadotropin-Releasing Hormone / pharmacology*
  • Green Fluorescent Proteins
  • Immunohistochemistry
  • Leuprolide / pharmacology
  • Luminescent Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Confocal
  • Organ Size / drug effects
  • Proto-Oncogene Proteins c-kit / physiology*
  • Seminiferous Tubules / physiology
  • Signal Transduction / physiology*
  • Sperm Count
  • Spermatogenesis / genetics
  • Spermatogonia / drug effects*
  • Spermatogonia / transplantation
  • Stem Cell Factor / genetics*
  • Stem Cell Factor / physiology*


  • Luminescent Proteins
  • Stem Cell Factor
  • Green Fluorescent Proteins
  • Gonadotropin-Releasing Hormone
  • Proto-Oncogene Proteins c-kit
  • Leuprolide