Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
Toxicologic Pathology
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Naciff, J. M.
Right arrow Articles by Daston, G. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Naciff, J. M.
Right arrow Articles by Daston, G. P.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Toxicogenomic Approach to Endocrine Disrupters: Identification of a Transcript Profile Characteristic of Chemicals with Estrogenic Activity

Jorge M. Naciff

Miami Valley Laboratories, The Procter and Gamble Company, Cincinnati, Ohio 45253, USA, naciff.jm{at}pg.com

George P. Daston

Miami Valley Laboratories, The Procter and Gamble Company, Cincinnati, Ohio 45253, USA

Public concerns have been raised in recent years over the possible adverse effects that may result from exposure to chemicals in the environment that have the potential to interfere with the normal function of the endocrine system in wildlife and humans ("endocrine disrupters"). Regulations have been established that require the testing of pesticides used in food crops and drinking water contaminants, for estrogenicity and other hormonal activities. In the United States, the U.S. EPA proposed the Endocrine Disrupter Screening Program, which consists of a Tier 1 screening battery of tests that is designed to identify chemicals capable of interacting with various hormonal systems, and different Tier 2 testing assays that are designed to verify and broaden the Tier 1 results. We identify 2 main problems with this approach: (1) the fact that the developmental stages that are the most susceptible to endocrine disruption are not represented in the screening tier, mainly because developmental effects tend to be latent, and there is no way to economically screen in developing models; and (2) the expense to screen each chemical to be included in this program. Thus, the need arises for an accurate, rapid, and cost effective method for assessing the potential endocrine activity of multiple chemicals during development. We hypothesize that the largely latent developmental effects of some endocrine disruptors are preceded by immediate changes in gene expression in the embryo and fetus. Therefore, an approach to assess the potential estrogenic (and other steroid hormonal) activity of different compounds is to identify those patterns of gene expression elicited in a tissue/organ exposed to these particular classes of chemicals. In this paper, the potential utility of such an approach for screening and better understanding of mechanism of action for specific chemicals with endocrine disrupter activities is presented, using as an example chemicals with estrogenic activity.

Key Words: Reproductive system of the female rat • gene expression profiling • microarrays • endocrine disrupters • 17-{alpha}-ethynyl estradiol • genistein • bisphenol A • uterotrophic assay.

References

  • Agnihotri, R., Crawford, H.C., Haro, H., Matrisian, L.M., Havrda, M.C., and Liaw, L. (2001). Osteopontin, a novel substrate for matrix metalloproteinase-3 (stromelysin-1) and matrix metalloproteinase-7 (matrilysin). J Biol Chem 276, 28261—7.[Abstract/Free Full Text]
  • Apparao, K.B., Murray, M.J., Fritz, M.A., Meyer, W.R., Chambers, A.F., Truong, P.R., and Lessey, B.A. (2001). Osteopontin and its receptor alphavbeta (3) integrin are coexpressed in the human endometrium during the menstrual cycle but regulated differentially. J Clin Endocrinol Metab 86, 4991—5000.[Abstract/Free Full Text]
  • Ashby, J., and Tinwell, H. (1998). Uterotrophic activity of bisphenol A in the immature rat. Environ Health Perspect 106, 719—20.[Web of Science][Medline] [Order article via Infotrieve]
  • Ashkar, S., Weber, G.F., Panoutsakopoulou, V., Sanchirico, M.E., Jansson, M., Zawaideh, S., Rittling, S.R., Denhardt, D.T., Glimcher, M.J., and Cantor, H. (2000). Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science 287, 860—4.[Abstract/Free Full Text]
  • Branham, W.S., Zehr, D.R., Chen, J.J., and Sheehan, D.M. (1988). Alterations in developing rat uterine cell populations after neonatal exposure to estrogens and antiestrogens. Teratology 38, 271—9.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Couse, J.F., Lindzey, J., Grandien, K., Gustafsson, J.A., and Korach, K.S. (1997). Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ER{alpha}-knockout mouse. Endocrinology 138, 4613—21.[Abstract/Free Full Text]
  • Diel, P., Schulz, T., Smolnikar, K., Strunck, E., Vollmer, G., and Michna, H. (2000). Ability of xeno- and phytoestrogens to modulate expression of estrogen-sensitive genes in rat uterus: estrogenicity profiles and uterotropic activity. J Steroid Biochem Mol Biol 73, 1—10.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Gong, X.Q., and Li, L. (2002). Dermo-1, a multifunctional basic helix-loop-helix protein, represses MyoD transactivation via the HLH domain, MEF2 interaction, and chromatin deacetylation. J Biol Chem 277, 12310—7.[Abstract/Free Full Text]
  • Gunther, E.C., Stone, D.J., Gerwien, R.W., Bento, P., and Heyes, M.P. (2003). Prediction of clinical drug efficacy by classification of drug-induced genomic expression profiles in vitro. Proc Natl Acad Sci USA 100, 9608—13.[Abstract/Free Full Text]
  • Hall, J.M., Couse, J.F., and Korach, K.S. (2001). The multifaceted mechanisms of estradiol and estrogen receptor signaling. J Biol Chem 276, 36869—72.[Free Full Text]
  • Hamadeh, H.K., Bushel, P.R., Jayadev, S., DiSorbo, O., Bennett, L., Li, L., Tennant, R., Stoll, R., Barrett, J.C., Paules, R.S., Blanchard, K., and Afshari, C.A. (2002a). Prediction of compound signature using high density gene expression profiling. Toxicol Sci 67, 232—40.[Abstract/Free Full Text]
  • Hamadeh, H.K., Bushel, P.R., Jayadev, S., Martin, K., DiSorbo, O., Sieber, S., Bennett, L., Tennant, R., Stoll, R., Barrett, J.C., Blanchard, K., Paules, R.S., and Afshari, C.A. (2002b). Gene expression analysis reveals chemical-specific profiles. Toxicol Sci 67, 219—31.[Abstract/Free Full Text]
  • Klinge, C.M. (2001). Estrogen receptor interaction with estrogen response elements. Nucleic Acids Res 29, 2905—19.[Abstract/Free Full Text]
  • Lee, M.S., Lowe, G., Flanagan, S., Kuchler, K., and Glackin, C.A. (2000). Human Dermo-1 has attributes similar to twist in early bone development. Bone 27, 591—602.[Medline] [Order article via Infotrieve]
  • Liaw, L., Birk, D.E., Ballas, C.B., Whitsitt, J.S., Davidson, J.M., and Hogan, B.L. (1998). Altered wound healing in mice lacking a functional osteopontin gene (spp1). J Clin Invest 101, 1468—78.[Web of Science][Medline] [Order article via Infotrieve]
  • Lockhart, D.J., Dong, H., Byrne, M.C., Follettie, M.T., Gallo, M.V., Chee, M.S., Mittmann, M., Wang, C., Kobayashi, M., Horton, H., and Brown, E.L. (1996). Expression monitoring by hybrydization to high-density oligonucleotide arrays. Nat Biotechnol 14, 1675—80.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • McLachlan, J.A., and Newbold, R.R. (1987). Estrogens and development. Environ Health Perspect 75, 25—7.[Web of Science][Medline] [Order article via Infotrieve]
  • Morimoto, I., Sasaki, Y., Ishida, S., Imai, K., and Tokino, T. (2002). Identification of the osteopontin gene as a direct target of TP53. Genes Chromosomes Cancer 33, 270—8.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Naciff, J.M., Jump, M.L., Torontali, S.M., Carr, G.J., Tiesman, J.P., Overmann, G.J., and Daston, G.P. (2002). Gene expression profile induced by 17 {alpha}-ethynyl estradiol, bisphenol a, and genistein in the developing female reproductive system of the rat. Toxicol Sci 68, 184—99.[Abstract/Free Full Text]
  • Naciff, J.M., Overmann, G.J., Torontali, S.M., Carr, G.J., Tiesman, J.P., Richardson, B.D., and Daston, G.P. (2003). Gene expression profile induced by 17 alpha-ethynyl estradiol in the prepubertal female reproductive system of the rat. Toxicol Sci 72, 314—30.[Abstract/Free Full Text]
  • Nilsson, S., Makela, S., Treuter, E., Tujague, M., Thomsen, J., Andersson, G., Enmark, E., Pettersson, K., Warner, M., and Gustafsson, J.A. (2001). Mechanisms of estrogen action. Physiol Rev 81, 1535—65.[Abstract/Free Full Text]
  • Noda, S., Sawaki, M., Shiraishi, K., Yamasaki, K., and Yamaguchi, R. (2002). Age-related changes of genital systems in the female Crj:CD (SD) IGS rats during sexual maturation. J Vet Med Sci 64, 315—9.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Nuwaysir, E.F., Bittner, M., Trent, J., Barrett, J.C., and Afshari, C.A. (1999). Microarrays and toxicology: the advent of toxicogenomics. Mol Carcinogenesis 24, 153—9.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Riggs, B.L., and Hartmann, L.C. (2003). Selective estrogen-receptor modulators mechanisms of action and application to clinical practice. N Engl J Med 348, 618—29.[Free Full Text]
  • Shang, Y., and Brown, M. (2002). Molecular determinants for the tissue specificity of SERMs. Science 295, 2465—8.[Abstract/Free Full Text]
  • Steiner, S., and Anderson, N.L. (2000). Expression profiling in toxicology: potential and limitations. Toxicol Lett 112—113, 467—71.[CrossRef]
  • Tamura, M., and Noda, M. (1999). Identification of DERMO-1 as a member of helix-loop-helix type transcription factors expressed in osteoblastic cells. J Cell Biochem 72, 167—76.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Thigpen, J.E., Setchell, K.D., Ahlmark, K.B., Locklear, J., Spahr, T., Caviness, G.F., Goelz, M.F., Haseman, J.K., Newbold, R.R., and Forsythe, D.B. (1999). Phytoestrogen content of purified, open- and closed-formula laboratory animal diets. Lab Anim Sci 49, 530—6.[Web of Science][Medline] [Order article via Infotrieve]
  • Toorop, A.I., Meijs-Roelofs, H.M., Kramer, P., and de Greef, W.J. (1984). Ovarian steroid concentrations in rats approaching first ovulation. J Endocrinol 100, 281—6.[Abstract/Free Full Text]
  • U. S. Environmental Protection Agency (1998 ). USA Environmental Protection Agency. Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) Final Report Chapter 5: Screening and Testing. <http://www.epa.gov/scipoly/oscpendo/history/finalrpt.htm >.
  • vom Saal, F.S., Timms, B.G., Montano, M.M., Palanza, P., Thayer, K.A., Nagel, S.C., Dhar, M.D., Ganjam, V.K., Parmigiani, S., and Welshons, W.V. (1997). Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses. Proc Natl Acad Sci USA 94, 2056—61.[Abstract/Free Full Text]
  • Yu, W.H., Woessner, J.F. Jr, McNeish, J.D., and Stamenkovic, I. (2002). CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling. Genes Dev 16, 307—23.[Abstract/Free Full Text]

Toxicologic Pathology, Vol. 32, No. 2 suppl, 59-70 (2004)
DOI: 10.1080/01926230490463812
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
M. Heneweer, R. Houtman, J. Poortman, M. Groot, C. Maliepaard, and A. Peijnenburg
Estrogenic Effects in the Immature Rat Uterus after Dietary Exposure to Ethinylestradiol and Zearalenone Using a Systems Biology Approach
Toxicol. Sci., September 1, 2007; 99(1): 303 - 314.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Naciff, J. M.
Right arrow Articles by Daston, G. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Naciff, J. M.
Right arrow Articles by Daston, G. P.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?