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Submitted on March 7, 2005
Accepted on September 8, 2005
Laboratory for Experimental Medicine & Endocrinology, Catholic University of Leuven, Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium; ESAT/SCD, Faculty of Engineering, Catholic University of Leuven, Kasteelpark Arenberg 10, B-3001 Heverlee, Belgium; VIB MicroArray Facility, UZ Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium; MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Old Dalkeith Road Edinburgh EH16 4TJ, Scotland, UK; Centre for Microbial and Plant Genetics, Faculty of Applied Bioscience and Engineering, Catholic University of Leuven, Kasteelpark Arenberg 20, B-3001 Heverlee, Belgium
* To whom correspondence should be addressed. E-mail: Guido.Verhoeven{at}med.kuleuven.be.
To unravel the molecular mechanisms mediating the effects of androgens on spermatogenesis, testicular gene expression was compared in mice with a Sertoli cell-selective androgen receptor knockout (SCARKO) and littermate controls on postnatal d 10. Microarray analysis identified 692 genes with significant differences in expression. Of these, 28 appeared to be "downregulated" and 12 "upregulated" at least 2-fold in SCARKOs as compared with controls. For 9 of the more than 2-fold downregulated genes androgen regulation was confirmed by treatment of wild type mice with an antiandrogen (flutamide). Some of them were previously described to be androgen-regulated or essential for spermatogenesis. Serine-type protease inhibitors were markedly overrepresented in this downregulated subgroup. A time study (d 8-d 20), followed by cluster analysis, allowed identification of distinct expression patterns of differentially expressed genes. Three genes with a pattern closely resembling that of Pem, a prototypical androgen-regulated gene expressed in Sertoli cells, were selected for confirmation by quantitative RT-PCR and for further analysis. The data confirm that the SCARKO model allows identification of novel androgen-regulated genes in the testis. Moreover, they suggest that protease inhibitors and other proteins related to tubular restructuring and cell junction dynamics may be controlled in part by androgens.
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