Skip Navigation



ToxSci Advance Access published online on June 9, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi219
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
87/1/97    most recent
kfi219v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Selvaraj, V.
Right arrow Articles by Cooke, P. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Selvaraj, V.
Right arrow Articles by Cooke, P. S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received February 3, 2005
Accepted June 1, 2005

Immunotoxiocology

Gene Expression Profiling of 17{beta}-Estradiol and Genistein Effects on Mouse Thymus

Vimal Selvaraj 1, David Bunick 1, Carrol Finnigan-Bunick 1, Rodney W. Johnson 2, Huixia Wang 3, Lei Liu 4, and Paul S. Cooke 5*

1 Department of Veterinary Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL 61802
2 Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61802
3 Department of Statistics, University of Illinois at Urbana-Champaign, Urbana, IL 61802
4 Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61802; W.M. Keck Center for Comparative and Functional Genomics, University of Illinois at Urbana-Champaign, Urbana, IL 61802
5 Department of Veterinary Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL 61802; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61802

* To whom correspondence should be addressed.
Paul S. Cooke, E-mail: p-cooke{at}uiuc.edu


  Abstract

Estrogen regulates thymic development and involution, and modulates immune function. Despite its critical role in thymus, as well as in autoimmune disorders, the mechanism by which estrogen affects the thymus is not well understood. We previously reported that the estrogenic soy isoflavone genistein, as well as 17{beta}-estradiol (E2), could induce thymic involution, but genistein effects were only partially mediated through estrogen receptors. To provide insights into mechanisms of estrogenic effects in the thymus, we investigated thymic gene expression changes induced by E2 (125 ng/day) and genistein (1500 ppm in feed) in weanling mice using high-density DNA arrays. We identified several E2 responsive genes involved in thymic development and thymocyte signaling during selection and maturation. Functional characterization indicated effects on genes involved in transcription, apoptosis and the cell cycle. This study also identified changes in several E2-regulated transcripts essential to maintain immune self-tolerance. E2 upregulated more genes than genistein, while genistein downregulated more genes than E2. Though each treatment regulated several genes not altered by the other, there was considerable overlap in the genes regulated by E2 and genistein. Changes in transcription factors and cell cycle factors were consistent with decreases in cell proliferation induced by both genistein and E2. As indicated by the regulation of non-E2-responsive genes, genistein also induced unique effects through non-estrogenic mechanisms. The specific downregulation of the CD4 co-receptor transcript by genistein was consistent with the decline of CD4+ thymocytes in genistein-treated mice in our previous study. This is the first study identifying E2 and genistein target genes in the thymus. These findings provide new mechanistic insights towards explaining estrogen action on thymocyte development, selection and maturation, as well as the effects of genistein on prenatal and neonatal thymic development and function.

Keywords: immune system; estrogen; T cells; soy; phytoestrogen; autoimmunity.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Nutr.Home page
P. S. Cooke, V. Selvaraj, and S. Yellayi
Genistein, Estrogen Receptors, and the Acquired Immune Response
J. Nutr., March 1, 2006; 136(3): 704 - 708.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.