title: The effect of a sertoli cell-selective knockout of the androgen receptor on testicular gene expression in prepubertal mice.
abstract: To unravel the molecular mechanisms mediating the effects of androgens on spermatogenesis, testicular gene expression was compared in mice with 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 down-regulated and 12 up-regulated at least 2-fold in SCARKOs compared with controls. For nine of the more than 2-fold down-regulated 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 down-regulated subgroup. A time study (d 8-20), 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 additional 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.
authors.affiliation: Laboratory for Experimental Medicine and Endocrinology, Catholic University of Leuven, Belgium.
authors.forename: Evi
authors.initials: E
authors.lastname: Denolet
authors.forename: Karel
authors.initials: K
authors.lastname: De Gendt
authors.forename: Joke
authors.initials: J
authors.lastname: Allemeersch
authors.forename: Kristof
authors.initials: K
authors.lastname: Engelen
authors.forename: Kathleen
authors.initials: K
authors.lastname: Marchal
authors.forename: Paul
authors.initials: P
authors.lastname: Van Hummelen
authors.forename: Karen A L
authors.initials: KA
authors.lastname: Tan
authors.forename: Richard M
authors.initials: RM
authors.lastname: Sharpe
authors.forename: Philippa T K
authors.initials: PT
authors.lastname: Saunders
authors.forename: Johannes V
authors.initials: JV
authors.lastname: Swinnen
authors.forename: Guido
authors.initials: G
authors.lastname: Verhoeven
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011944:Receptors, Androgen / Q000235:genetics*; D012708:Sertoli Cells / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000728:Androgens; D018398:Homeodomain Proteins; D011944:Receptors, Androgen; D014157:Transcription Factors; C498048:Rhox5 protein, mouse