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.
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| Abstract |
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.
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| Authors | K T Blanchard, J Lee, K Boekelheide |
| Journal | Endocrinology (Endocrinology) Vol. 139 Issue 1 Pg. 236-44 (Jan 1998) ISSN: 0013-7227 [Print] United States |
| PMID | 9421420 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
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