Leuprolide, a gonadotropin-releasing hormone agonist, reestablishes spermatogenesis after 2,5-hexanedione-induced irreversible testicular injury in the rat, resulting in normalized stem cell factor expression.
2,5-Hexanedione (2,5-HD) exposure in the rat produces irreversible testicular atrophy, a model of human male infertility that can be used for mechanistic and therapeutic studies. Following testicular injury by 2,5-HD, stem cell factor (SCF), a Sertoli cell-derived growth factor that binds the c-kit receptor on spermatogonia, is altered in its expression, changing from predominantly membrane SCF to predominantly soluble SCF. The goals of this study were 2-fold: first, evaluate leuprolide, a GnRH agonist, as a therapy for 2,5-HD-induced testicular atrophy, and second, examine changes in SCF expression during testicular injury and following recovery from injury. Rats exposed to 2,5-HD showed a nearly complete testicular atrophy that could be reversed by leuprolide therapy. Using RT-PCR, preferential expression of membrane SCF was associated with spermatogenesis, whereas soluble SCF expression was associated with atrophy. In conclusion, 2,5-HD exposure altered the form of SCF expressed and disrupted spermatogenesis; leuprolide therapy allowed recovery of spermatogenesis, which correlated with a normalization in growth factor expression in an otherwise irreversibly atrophic testis.
Blanchard
K T
KT
Boehringer-Ingelheim Research and Development Center, Ridgefield, Connecticut 06877, USA.
Lee
J
J
Boekelheide
K
K
D000818:Animals; D001284:Atrophy; D006588:Hexanones / Q000633:toxicity*; D016729:Leuprolide / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013091:Spermatogenesis / Q000187:drug effects*; D019089:Stem Cell Factor / Q000096:biosynthesis*; D013737:Testis / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology
D006588:Hexanones; D019089:Stem Cell Factor; C011269:2,5-hexanedione; D016729:Leuprolide