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This version published online on September 11, 2003
Endocrinology, doi:10.1210/en.2003-0735
A more recent version of this article appeared on December 1, 2003
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Submitted on June 11, 2003
Accepted on August 26, 2003

Reduced Intratesticular Testosterone Concentration Alters the Polymerization State of the Sertoli Cell Intermediate Filament Cytoskeleton by Degradation of Vimentin

Matthew D. Show1*, Matthew D. Anway1, Janet S. Folmer1, and Barry R. Zirkin1

1 Division of Reproductive Biology, Department of Biochemistry and Molecular Biology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205.

* To whom correspondence should be addressed. E-mail: mshow{at}jhsph.edu.

The Sertoli cell intermediate filament cytoskeleton is composed of the type III family member vimentin. The distribution of Sertoli cell vimentin varies with the stage of spermatogenesis, with shortening of the filaments at Stages VII-VIII, the stages of spermiation. Experimental reduction in intratesticular testosterone concentration also results in the sloughing of advanced spermatids from the Sertoli cells, as well as in the apoptotic death of spermatocytes. We hypothesized that alteration of the distribution of Sertoli cell vimentin might play a role in the loss of germ cells that occurs in response to reduced intratesticular testosterone. To test this hypothesis, intratesticular testosterone was reduced by implanting LH-suppressive Silastic capsules containing testosterone and estradiol into adult rats for 8 weeks. Immunohistochemical analyses revealed that, in response to the implants, the vimentin cytoskeleton collapsed around the Sertoli cell nuclei at all stages of the cycle, losing the extensive branching and structure normally seen at most stages of the cycle. Western blots of isolated Sertoli cells revealed that protein levels did not differ significantly between control and TE-treated rats. However, Sertoli cell fractions containing the vimentin monomer revealed that vimentin was cleaved into 4-5 fragments in Sertoli cells in response to the implants, suggestive of proteolysis. These results indicate that, in response to reduced intratesticular testosterone, the vimentin cytoskeleton of the Sertoli cell collapses to a perinuclear localization, and suggest that this collapse is associated with, and perhaps caused by, the degradation of the vimentin monomer rather than by loss of its expression.


Key words: Sertoli cells • testosterone • vimentin • intermediate filaments




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