Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
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 ISI Web of Science
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 arrow Search for citing articles in:
ISI Web of Science (24)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Buchanan, D. L.
Right arrow Articles by Cooke, P. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Buchanan, D. L.
Right arrow Articles by Cooke, P. S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Toxicological Sciences 57, 302-311 (2000)
Copyright © 2000 by the Society of Toxicology

Reproductive and Developmental Toxicology

Antiestrogenic Effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Mouse Uterus: Critical Role of the Aryl Hydrocarbon Receptor in Stromal Tissue

David L. Buchanan*,1, Tomomi Sato*, Richard E. Peterson{dagger} and Paul S. Cooke*,2

* Department of Veterinary Biosciences, University of Illinois, Urbana, Illinois 61802; and {dagger} School of Pharmacy and Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin 53706

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the role of aryl hydrocarbon receptor (AhR) in estradiol (E2)-induced uterine epithelial mitogenic activity and secretory protein mRNA expression were determined. Ovariectomized wild-type (wt) and AhR-knockout (AhRKO) mice received oil, E2, or 5 µg/kg TCDD+E2. E2 stimulated similar large increases in the uterine epithelial labeling index (LI) and mRNA abundance for the E2-dependent epithelial secretory protein, lactoferrin (LF), in both wt and AhRKO mice. However, uterine epithelial LI and LF mRNA were significantly reduced by TCDD+E2 in wt but not AhRKO mice. To determine the roles of stromal and epithelial AhR in the TCDD effect, uterine stroma and epithelium from AhRKO and wt mice were enzymatically separated and recombined into four types of tissue recombinants that either contained or lacked AhR in one or more tissue compartments. Tissue recombinants were grafted into nude mice, which were later ovariectomized and given oil, E2, or TCDD+E2. Epithelial LI was significantly reduced by TCDD in grafts containing stromal AhR, regardless of epithelial AhR status. However, LI was unaffected by TCDD in grafts lacking stromal AhR, even when epithelial AhR was present. Thus, TCDD inhibits E2-induced uterine epithelial mitogenic and secretory activity, and this requires AhR. Anti-proliferative effects of TCDD on uterine epithelia appear to be mediated indirectly through stromal AhR, suggesting that liganded AhR alters epithelial function by disrupting normal E2-induced stromal activity. This is the first demonstration that TCDD impairs uterine epithelial function by altering normal stromal-epithelial interactions in vivo.

Key Words: mouse; estrogen receptor-{alpha}; mitogenesis; epithelium; stroma; antiestrogen; lactoferrin; TCDD; dioxin; uterus; aryl hydrocarbon receptor.


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
 EndocrinologyHome page
T.-C. E. Lin, S.-C. Chien, P.-C. Hsu, and L.-A. Li
Mechanistic Study of Polychlorinated Biphenyl 126-Induced CYP11B1 and CYP11B2 Up-Regulation
Endocrinology, March 1, 2006; 147(3): 1536 - 1544.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. Sato, G. Wang, M. P. Hardy, T. Kurita, G. R. Cunha, and P. S. Cooke
Role of Systemic and Local IGF-I in the Effects of Estrogen on Growth and Epithelial Proliferation of Mouse Uterus
Endocrinology, July 1, 2002; 143(7): 2673 - 2679.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
B. G. Timms, R. E. Peterson, and F. S. vom Saal
2,3,7,8-Tetrachlorodibenzo-p-dioxin Interacts with Endogenous Estradiol to Disrupt Prostate Gland Morphogenesis in Male Rat Fetuses
Toxicol. Sci., June 1, 2002; 67(2): 264 - 274.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
D. L. Buchanan, S. Ohsako, C. Tohyama, P. S. Cooke, and T. Iguchi
Dioxin Inhibition of Estrogen-Induced Mouse Uterine Epithelial Mitogenesis Involves Changes in Cyclin and Transforming Growth Factor-{beta} Expression
Toxicol. Sci., March 1, 2002; 66(1): 62 - 68.
[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.