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Endocrinology Vol. 139, No. 1 236-244
Copyright © 1998 by The Endocrine Society

ARTICLES

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 Expression1

Kerry T. Blanchard, Jeongwu Lee and Kim Boekelheide

Boehringer-Ingelheim Research and Development Center (K.T.B.), Ridgefield, Connecticut 06877; and Department of Pathology and Laboratory Medicine, Brown University (J.L., K.B.), Providence, Rhode Island 01912

Address all correspondence and requests for reprints to: Kim Boekelheide, Department of Pathology and Laboratory Medicine, Brown University, Box G-B518, Providence, Rhode Island 02912. E-mail: kim_boekelheide{at}brown.edu

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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