期刊
JOURNAL OF TOXICOLOGICAL SCIENCES
卷 37, 期 2, 页码 287-295出版社
JAPANESE SOC TOXICOLOGICAL SCIENCES
DOI: 10.2131/jts.37.287
关键词
Leydig cells; Diethylstilbestrol; 17 beta-estradiol; Gene Ontology; DNA repair; Apoptosis
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [19890144, 21791037]
- Grants-in-Aid for Scientific Research [19890144, 21791037, 23390386] Funding Source: KAKEN
This study investigated the deleterious effects of the synthetic non-steroidal estrogen diethylstilbestrol (DES) on testicular Leydig cells and compared these effects with those of the natural estrogen 17 beta-estradiol (E2). For that purpose, we performed microarray analysis of a mouse Leydig cell line (TTE1) treated with these estrogens, followed by Gene Ontology (GO) analysis and parametric analysis of gene set enrichment (PAGE). Most notably, GO analysis revealed a significant decrease in the biological processes of the GO categories DNA repair and apoptotic program in DES-exposed cells. PAGE showed that cell death, which is a superior GO category including apoptosis in the GO tree structure, significantly decreased in DES-exposed cells but significantly increased in E2-exposed cells. Interestingly, only 2 genes (Tia1 and Gas1) with altered expression patterns in the cell death category were common between DES- and E2-treated cells. The downregulation of apoptotic cell death pathways and DNA repair capability of DES-exposed cells implies that DES promotes carcinogenic processes more strongly than E2 does. These findings suggest that molecular events that occur following DES and E2 treatments differ substantially in Leydig cells, and that the effects of synthetic estrogen and natural estrogen differ more substantially than previously suspected.
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