Germ cell apoptosis in the testes of Sprague Dawley rats following testosterone withdrawal by ethane 1,2-dimethanesulfonate administration: relationship to Fas?
Germ cell apoptosis, which occurs normally during spermatogenesis, increases after testosterone withdrawal from the testis. The molecular mechanism by which this occurs remains uncertain. The Fas system has been implicated as a possible key regulator of apoptosis in various cells: binding of Fas ligand (FasL), a type II transmembrane protein, to Fas, a type I transmembrane receptor protein, triggers apoptosis in cells expressing Fas. Recently, Fas has been localized to germ cells, and FasL to Sertoli cells, within the rat testis. We hypothesized that Fas protein content would rise in response to reduced levels of testosterone as part of a suicide pathway that would result in germ cell apoptosis. To test this hypothesis, ethane 1,2-dimethanesulfonate (EDS), a Leydig cell toxicant, was used to kill Leydig cells and thus reduce intratesticular testosterone levels in Sprague Dawley rats. Apoptosis was examined in situ and biochemically, and Fas protein content in the testis was monitored by Western blot analysis. We show that EDS injection results in the following sequence of events: apoptotic death of Leydig cells by a mechanism that does not involve Fas; reduced testosterone; increased testicular Fas content; and germ cell apoptosis. These results suggest that Fas may play a role in the apoptotic death of germ cells that results from reduced intratesticular testosterone levels, and that testosterone may play a role in germ cell survival via its suppression of Fas.
Nandi
S
S
Division of Reproductive Biology, Department of Biochemistry, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, Maryland 21205, USA.
Banerjee
P P
PP
Zirkin
B R
BR
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053938:DNA Fragmentation; D053222:Fas Ligand Protein; D007985:Leydig Cells / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology*; D008698:Mesylates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000737:chemistry; D013739:Testosterone / Q000008:administration & dosage / Q000502:physiology*
D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D008698:Mesylates; D013739:Testosterone; C002994:ethylene dimethanesulfonate