title: Leydig cells contribute to the inhibition of spermatogonial differentiation after irradiation of the rat.
abstract: Irradiation with 6 Gy produces a complete block of spermatogonial differentiation in LBNF1 rats that would be permanent without treatment. Subsequent suppression of gonadotropins and testosterone (T) restores differentiation to the spermatocyte stage; however, this process requires 6 weeks. We evaluated the role of Leydig cells (LCs) in maintenance of the block in spermatogonial differentiation after exposure to radiation by specifically eliminating functional LCs with ethane dimethane sulfonate (EDS). EDS (but not another alkylating agent), given at 10 weeks after irradiation, induced spermatogonial differentiation in 24% of seminiferous tubules 2 weeks later. However, differentiation became blocked again at 4 weeks as LCs recovered. When EDS was followed by treatment with GnRH antagonist and flutamide, sustained spermatogonial differentiation was induced in >70% of tubules within 2 weeks. When EDS was followed by GnRH antagonist plus exogenous T, which also inhibits LC recovery but restores follicle stimulating hormone (FSH) levels, the spermatogonial differentiation was again rapid but transient. These results confirm that the factors that block spermatogonial differentiation are indirectly regulated by T, and probably FSH, and that adult and possibly immature LCs contribute to the production of such inhibitory factors. We tested whether insulin-like 3 (INSL3), a LC-produced protein whose expression correlated with the block in spermatogonial differentiation, was indeed responsible for the block by injecting synthetic INSL3 into the testes and knocking down its expression in vivo with siRNA. Neither treatment had any effect on spermatogonial differentiation. The Leydig cell products that contribute to the inhibition of spermatogonial differentiation in irradiated rats remain to be elucidated.
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: G
authors.initials: G
authors.lastname: Shetty
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: C C Y
authors.initials: CC
authors.lastname: Weng
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Shao
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Meistrich
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D005485:Flutamide / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D008297:Male; D008698:Mesylates / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D011829:Radiation Dosage; D051381:Rats; D012671:Seminiferous Tubules / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D013091:Spermatogenesis / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D013093:Spermatogonia / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D013739:Testosterone / Q000494:pharmacology
chemical_list: D000726:Androgen Antagonists; D008698:Mesylates; D009842:Oligopeptides; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D005485:Flutamide; C002994:ethylene dimethanesulfonate; C109238:acyline
keywords: ethane dimethane sulfonate; irradiation; leydig cell; spermatogonia; testosterone