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Publication : Testosterone inhibits spermatogonial differentiation in juvenile spermatogonial depletion mice.

First Author  Shetty G Year  2001
Journal  Endocrinology Volume  142
Issue  7 Pages  2789-95
PubMed ID  11415997 Mgi Jnum  J:71935
Mgi Id  MGI:2151286 Doi  10.1210/endo.142.7.8237
Citation  Shetty G, et al. (2001) Testosterone inhibits spermatogonial differentiation in juvenile spermatogonial depletion mice. Endocrinology 142(7):2789-95
abstractText  The juvenile spermatogonial depletion (jsd) mutation results in spermatogonial arrest after the first wave of spermatogenesis. In homozygous jsd mice in a hybrid background (C3HxB6) that were identified with microsatellite markers, the percentage of tubules showing differentiating germ cells [tubule differentiation index (TDI)] rapidly decreased after 7 weeks of age with a correlative increase in the intratesticular testosterone (ITT) levels. Treatment with a GnRH antagonist, Cetrorelix, suppressed ITT and stimulated spermatogonial differentiation at the end of treatment. When treated mice were killed 5-13.3 weeks after the end of treatment, the ITT progressively increased, and the TDI progressively declined, but there was a transient appearance of tubules with mature spermatids. To delineate the role of testosterone (T) in spermatogonial arrest, we gave 7.6-week-old jsd mice exogenous T and/or the androgen receptor antagonist flutamide with or without GnRH antagonist for 4 weeks. Flutamide alone moderately stimulated spermatogonial differentiation (TDI = 30%). GnRH antagonist increased the TDI to 73%, and the addition of flutamide to the GnRH antagonist treatment further increased it to 95%. When T was combined with GnRH antagonist treatment, ITT was increased, and the TDI was reduced to 7%. Addition of flutamide to this combination reversed the T inhibition of GnRH antagonist stimulation of spermatogonial differentiation to a TDI of 57%. ITT levels showed a good negative correlation to the TDI obtained with various treatments, but no such correlation was observed for FSH or LH levels. The results indicate that T inhibits the ability of spermatogonia to differentiate in jsd mice through an androgen receptor-mediated process.
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