Uterine temporal response to acute exposure to 17alpha-ethinyl estradiol in the immature rat
The rat uterus responds to acute estrogen treatment with a series of well-characterized physiological responses; however, the gene expression changes required to elicit these responses have not been fully characterized. In order to understand early events induced by estrogen exposure in vivo, we eva...
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| Veröffentlicht in: | Toxicological sciences 2007-06, Vol.97 (2), p.467 |
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| creator | Naciff, Jorge M Overmann, Gary J Torontali, Suzanne M Carr, Gregory J Khambatta, Zubin S Tiesman, Jay P Richardson, Brian D Daston, George P |
| description | The rat uterus responds to acute estrogen treatment with a series of well-characterized physiological responses; however, the gene expression changes required to elicit these responses have not been fully characterized. In order to understand early events induced by estrogen exposure in vivo, we evaluated the temporal gene expression in the uterus of the immature rat after a single dose of 17 alpha-ethinyl estradiol (EE) by microarray analysis, evaluating the expression of 15,923 genes. Immature 20-day-old rats were exposed to a single dose of EE (10 microg/kg), and the effects on uterine histology, weight, and gene expression were determined after 1, 2, 8, 24, 48, 72, and 96 h. EE induced changes in the expression of 3867 genes, at least at one time point (p < or = 0.0001), and at least 1.5-fold (up- or downregulated). Specifically, the expression of 8, 116, 3030, 2076, 381, 445, and 125 genes was modified at 1, 2, 8, 24, 48, 72, or 96 h after exposure to EE, respectively (p < or = 0.0001, t-test). At the tissue and organ level, a clear uterotrophic response was elicited by EE after only 8 h, reaching a maximum after 24 h and remaining detectable even after 96 h of exposure. The uterine phenotypic changes were induced by sequential changes in the transcriptional status of a large number of genes, in a program that involves multiple molecular pathways. Using the Gene Ontology to better understand the temporal response to estrogen exposure, we determined that the earliest changes were in the expression of genes whose products are involved in transcriptional regulation and signal transduction, followed by genes implicated in protein synthesis, energy utilization, solute transport, cell proliferation and differentiation, tissue remodeling, and immunological responses among other pathways. The compendium of genes here presented represents a comprehensive compilation of estrogen-responsive genes involved in the uterotrophic response. |
| format | Article |
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In order to understand early events induced by estrogen exposure in vivo, we evaluated the temporal gene expression in the uterus of the immature rat after a single dose of 17 alpha-ethinyl estradiol (EE) by microarray analysis, evaluating the expression of 15,923 genes. Immature 20-day-old rats were exposed to a single dose of EE (10 microg/kg), and the effects on uterine histology, weight, and gene expression were determined after 1, 2, 8, 24, 48, 72, and 96 h. EE induced changes in the expression of 3867 genes, at least at one time point (p < or = 0.0001), and at least 1.5-fold (up- or downregulated). Specifically, the expression of 8, 116, 3030, 2076, 381, 445, and 125 genes was modified at 1, 2, 8, 24, 48, 72, or 96 h after exposure to EE, respectively (p < or = 0.0001, t-test). At the tissue and organ level, a clear uterotrophic response was elicited by EE after only 8 h, reaching a maximum after 24 h and remaining detectable even after 96 h of exposure. The uterine phenotypic changes were induced by sequential changes in the transcriptional status of a large number of genes, in a program that involves multiple molecular pathways. Using the Gene Ontology to better understand the temporal response to estrogen exposure, we determined that the earliest changes were in the expression of genes whose products are involved in transcriptional regulation and signal transduction, followed by genes implicated in protein synthesis, energy utilization, solute transport, cell proliferation and differentiation, tissue remodeling, and immunological responses among other pathways. The compendium of genes here presented represents a comprehensive compilation of estrogen-responsive genes involved in the uterotrophic response.</description><identifier>ISSN: 1096-6080</identifier><identifier>PMID: 17351261</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Body Weight - drug effects ; Cell Line ; Data Interpretation, Statistical ; Estrogens - metabolism ; Ethinyl Estradiol - toxicity ; Female ; Gene Expression - drug effects ; Genes, Immediate-Early - drug effects ; Male ; Oligonucleotide Array Sequence Analysis ; Organ Size - drug effects ; Phenotype ; Rats ; Rats, Sprague-Dawley ; Reproduction - drug effects ; Reverse Transcriptase Polymerase Chain Reaction ; Uterus - drug effects ; Uterus - pathology</subject><ispartof>Toxicological sciences, 2007-06, Vol.97 (2), p.467</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17351261$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Naciff, Jorge M</creatorcontrib><creatorcontrib>Overmann, Gary J</creatorcontrib><creatorcontrib>Torontali, Suzanne M</creatorcontrib><creatorcontrib>Carr, Gregory J</creatorcontrib><creatorcontrib>Khambatta, Zubin S</creatorcontrib><creatorcontrib>Tiesman, Jay P</creatorcontrib><creatorcontrib>Richardson, Brian D</creatorcontrib><creatorcontrib>Daston, George P</creatorcontrib><title>Uterine temporal response to acute exposure to 17alpha-ethinyl estradiol in the immature rat</title><title>Toxicological sciences</title><addtitle>Toxicol Sci</addtitle><description>The rat uterus responds to acute estrogen treatment with a series of well-characterized physiological responses; however, the gene expression changes required to elicit these responses have not been fully characterized. In order to understand early events induced by estrogen exposure in vivo, we evaluated the temporal gene expression in the uterus of the immature rat after a single dose of 17 alpha-ethinyl estradiol (EE) by microarray analysis, evaluating the expression of 15,923 genes. Immature 20-day-old rats were exposed to a single dose of EE (10 microg/kg), and the effects on uterine histology, weight, and gene expression were determined after 1, 2, 8, 24, 48, 72, and 96 h. EE induced changes in the expression of 3867 genes, at least at one time point (p < or = 0.0001), and at least 1.5-fold (up- or downregulated). Specifically, the expression of 8, 116, 3030, 2076, 381, 445, and 125 genes was modified at 1, 2, 8, 24, 48, 72, or 96 h after exposure to EE, respectively (p < or = 0.0001, t-test). At the tissue and organ level, a clear uterotrophic response was elicited by EE after only 8 h, reaching a maximum after 24 h and remaining detectable even after 96 h of exposure. The uterine phenotypic changes were induced by sequential changes in the transcriptional status of a large number of genes, in a program that involves multiple molecular pathways. Using the Gene Ontology to better understand the temporal response to estrogen exposure, we determined that the earliest changes were in the expression of genes whose products are involved in transcriptional regulation and signal transduction, followed by genes implicated in protein synthesis, energy utilization, solute transport, cell proliferation and differentiation, tissue remodeling, and immunological responses among other pathways. The compendium of genes here presented represents a comprehensive compilation of estrogen-responsive genes involved in the uterotrophic response.</description><subject>Animals</subject><subject>Body Weight - drug effects</subject><subject>Cell Line</subject><subject>Data Interpretation, Statistical</subject><subject>Estrogens - metabolism</subject><subject>Ethinyl Estradiol - toxicity</subject><subject>Female</subject><subject>Gene Expression - drug effects</subject><subject>Genes, Immediate-Early - drug effects</subject><subject>Male</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Organ Size - drug effects</subject><subject>Phenotype</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reproduction - drug effects</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Uterus - drug effects</subject><subject>Uterus - pathology</subject><issn>1096-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1j8lqwzAURbVoadK0v1D0AwbJsp6lZQmdINBNuiuEF_kJq3gQkgzN3zedVhcOhwP3gq2lsFCBMGLFrnP-EEJKEPaKrWSrtKxBrtn7W6EUJuKFxjgnHHiiHOcpn8nM0S2FOH3GOS_ph8gWh9hjRaUP02nglEvCLswDDxMvPfEwjli-5YTlhl16HDLd_u2G7R8f9tvnavf69LK931VRN7JqagMOa20tGtO2SioACVZ34BR4UNa6VhvRgDiaxouz6Dxqq5V31jlNasPufrNxOY7UHWIKI6bT4f-l-gJif01B</recordid><startdate>200706</startdate><enddate>200706</enddate><creator>Naciff, Jorge M</creator><creator>Overmann, Gary J</creator><creator>Torontali, Suzanne M</creator><creator>Carr, Gregory J</creator><creator>Khambatta, Zubin S</creator><creator>Tiesman, Jay P</creator><creator>Richardson, Brian D</creator><creator>Daston, George P</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>200706</creationdate><title>Uterine temporal response to acute exposure to 17alpha-ethinyl estradiol in the immature rat</title><author>Naciff, Jorge M ; Overmann, Gary J ; Torontali, Suzanne M ; Carr, Gregory J ; Khambatta, Zubin S ; Tiesman, Jay P ; Richardson, Brian D ; Daston, George P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p541-4286ca2599a8877313661695d6c36f6399c7580460b84f0259cfa5953fc9cc5e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Body Weight - drug effects</topic><topic>Cell Line</topic><topic>Data Interpretation, Statistical</topic><topic>Estrogens - metabolism</topic><topic>Ethinyl Estradiol - toxicity</topic><topic>Female</topic><topic>Gene Expression - drug effects</topic><topic>Genes, Immediate-Early - drug effects</topic><topic>Male</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Organ Size - drug effects</topic><topic>Phenotype</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reproduction - drug effects</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Uterus - drug effects</topic><topic>Uterus - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Naciff, Jorge M</creatorcontrib><creatorcontrib>Overmann, Gary J</creatorcontrib><creatorcontrib>Torontali, Suzanne M</creatorcontrib><creatorcontrib>Carr, Gregory J</creatorcontrib><creatorcontrib>Khambatta, Zubin S</creatorcontrib><creatorcontrib>Tiesman, Jay P</creatorcontrib><creatorcontrib>Richardson, Brian D</creatorcontrib><creatorcontrib>Daston, George P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Toxicological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Naciff, Jorge M</au><au>Overmann, Gary J</au><au>Torontali, Suzanne M</au><au>Carr, Gregory J</au><au>Khambatta, Zubin S</au><au>Tiesman, Jay P</au><au>Richardson, Brian D</au><au>Daston, George P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Uterine temporal response to acute exposure to 17alpha-ethinyl estradiol in the immature rat</atitle><jtitle>Toxicological sciences</jtitle><addtitle>Toxicol Sci</addtitle><date>2007-06</date><risdate>2007</risdate><volume>97</volume><issue>2</issue><spage>467</spage><pages>467-</pages><issn>1096-6080</issn><abstract>The rat uterus responds to acute estrogen treatment with a series of well-characterized physiological responses; however, the gene expression changes required to elicit these responses have not been fully characterized. In order to understand early events induced by estrogen exposure in vivo, we evaluated the temporal gene expression in the uterus of the immature rat after a single dose of 17 alpha-ethinyl estradiol (EE) by microarray analysis, evaluating the expression of 15,923 genes. Immature 20-day-old rats were exposed to a single dose of EE (10 microg/kg), and the effects on uterine histology, weight, and gene expression were determined after 1, 2, 8, 24, 48, 72, and 96 h. EE induced changes in the expression of 3867 genes, at least at one time point (p < or = 0.0001), and at least 1.5-fold (up- or downregulated). Specifically, the expression of 8, 116, 3030, 2076, 381, 445, and 125 genes was modified at 1, 2, 8, 24, 48, 72, or 96 h after exposure to EE, respectively (p < or = 0.0001, t-test). At the tissue and organ level, a clear uterotrophic response was elicited by EE after only 8 h, reaching a maximum after 24 h and remaining detectable even after 96 h of exposure. The uterine phenotypic changes were induced by sequential changes in the transcriptional status of a large number of genes, in a program that involves multiple molecular pathways. Using the Gene Ontology to better understand the temporal response to estrogen exposure, we determined that the earliest changes were in the expression of genes whose products are involved in transcriptional regulation and signal transduction, followed by genes implicated in protein synthesis, energy utilization, solute transport, cell proliferation and differentiation, tissue remodeling, and immunological responses among other pathways. The compendium of genes here presented represents a comprehensive compilation of estrogen-responsive genes involved in the uterotrophic response.</abstract><cop>United States</cop><pmid>17351261</pmid></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Body Weight - drug effects Cell Line Data Interpretation, Statistical Estrogens - metabolism Ethinyl Estradiol - toxicity Female Gene Expression - drug effects Genes, Immediate-Early - drug effects Male Oligonucleotide Array Sequence Analysis Organ Size - drug effects Phenotype Rats Rats, Sprague-Dawley Reproduction - drug effects Reverse Transcriptase Polymerase Chain Reaction Uterus - drug effects Uterus - pathology |
| title | Uterine temporal response to acute exposure to 17alpha-ethinyl estradiol in the immature rat |
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