| Summary: | 博士 === 國防醫學院 === 生命科學研究所 === 100 === Klinefelter syndrome (KS), characterized by the presence of one extra X chromosome in men, is a major genetic cause of male infertility. Germ cell degeneration in KS patients is thought to be the consequences of over-expression of some genes on the X chromosome. However, the identity of these genes and the underlying mechanisms remain unclear. TEX11 (Testis-expressed 11) is an X-chromosome encoded germ-cell specific protein that is expressed most abundantly in spermatogonia and early spermatocytes in the testes. We used yeast two-hybrid screen to search for TEX11 interacting partners and identified HPIP (Hematopoietic BPX-Interacting Protein) which anchors estrogen receptors (ERs) to the cytoskeleton and modulates their functions. We found that mouse spermatogonial stem cells expressed Tex11, Hpip, and Esr2, but not Esr1. In cultured cells TEX11 competed with ERb for the binding to HPIP. Upon treatment with 17b-estradiol (E2) or an ERb agonist DPN, TEX11 promoted the nuclear translocation of ERb and enhanced its transcriptional activities. On the other hand, TEX11 suppressed the nongenomic activities of ERb in the cytoplasm, as indicated by the reduced phosphorylation of AKT and ERK signaling molecules. Over-expression of TEX11 in mouse germ-cell derived GC-1 and GC-2 cells suppressed the cell proliferation and the expression of cFos, Ccnd1, and Ccnb1 that were stimulated by E2 or DPN, and elevated the expression level of the proapoptotic Bax gene. The negative effect of TEX11 on cell proliferation suggests that increased expression of TEX11 in the germ cells may partially contribute to the spermatogenic defect observed in KS patients.
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