BENZO(A)PYRENE DECREASES BRAIN AND OVARIAN AROMATASE mRNA EXPRESSION IN FUNDULUS HETEROCLITUS
Identifieur interne : 000027 ( Pmc/Curation ); précédent : 000026; suivant : 000028BENZO(A)PYRENE DECREASES BRAIN AND OVARIAN AROMATASE mRNA EXPRESSION IN FUNDULUS HETEROCLITUS
Auteurs : Wu Dong ; Lu Wang ; Cammi Thornton ; Brian E. Scheffler [États-Unis] ; Kristine L. WillettSource :
- Aquatic toxicology (Amsterdam, Netherlands) [ 0166-445X ] ; 2008.
Abstract
The higher molecular weight polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BaP) are typically associated with genotoxicity, however, newer evidence suggests that these compounds may also act as endocrine system disruptors. We hypothesized that altered expression of the P450 enzyme aromatase genes could be a target for reproductive or developmental dysfunction caused by BaP exposure. Aromatase is at least partially responsible for estrogen homeostasis by converting androgens into estrogens. In fish, there are two isoforms of aromatase, a predominantly ovarian form, CYP19A1, and a brain form, CYP19A2. CYP19 mRNA expression was measured following BaP exposure (0, 10, 100 µg/L waterborne for 10 or 15 days) in
Url:
DOI: 10.1016/j.aquatox.2008.05.006
PubMed: 18571745
PubMed Central: 2530897
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Wu Dong<affiliation><nlm:aff id="A1">Department of Pharmacology and Environmental Toxicology Research Program, School of Pharmacy, University of Mississippi, 38677</nlm:aff>
<wicri:noCountry code="subfield">38677</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A1">Department of Pharmacology and Environmental Toxicology Research Program, School of Pharmacy, University of Mississippi, 38677</nlm:aff>
<wicri:noCountry code="subfield">38677</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A1">Department of Pharmacology and Environmental Toxicology Research Program, School of Pharmacy, University of Mississippi, 38677</nlm:aff>
<wicri:noCountry code="subfield">38677</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A1">Department of Pharmacology and Environmental Toxicology Research Program, School of Pharmacy, University of Mississippi, 38677</nlm:aff>
<wicri:noCountry code="subfield">38677</wicri:noCountry>
</affiliation>
Le document en format XML
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<author><name sortKey="Dong, Wu" sort="Dong, Wu" uniqKey="Dong W" first="Wu" last="Dong">Wu Dong</name>
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<series><title level="j">Aquatic toxicology (Amsterdam, Netherlands)</title>
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<front><div type="abstract" xml:lang="en"><p id="P1">The higher molecular weight polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BaP) are typically associated with genotoxicity, however, newer evidence suggests that these compounds may also act as endocrine system disruptors. We hypothesized that altered expression of the P450 enzyme aromatase genes could be a target for reproductive or developmental dysfunction caused by BaP exposure. Aromatase is at least partially responsible for estrogen homeostasis by converting androgens into estrogens. In fish, there are two isoforms of aromatase, a predominantly ovarian form, CYP19A1, and a brain form, CYP19A2. CYP19 mRNA expression was measured following BaP exposure (0, 10, 100 µg/L waterborne for 10 or 15 days) in <italic>Fundulus</italic>
adults, juveniles and embryos by <italic>in situ</italic>
hybridization. The CYP19A1 expression was significantly decreased after BaP exposure in the 3 month old <italic>Fundulus</italic>
immature oocytes, but BaP did not affect CYP19A1 expression at any stage in adult oocytes. In embryo brains, BaP significantly decreased CYP19A2 compared to controls by 3.6-fold at 14 days post-fertilization. In adults, CYP19A2 expression was decreased significantly in the pituitary and hypothalamus (81% and 85% of controls, respectively). Promoter regions of <italic>Fundulus</italic>
CYP19s were cloned, and putative response elements in the CYP19A1 and CYP19A2 promoters such as CRE, AhR and ERE may be involved in BaP-mediated changes in CYP19 expression. In order to compare the mechanism of BaP-mediated inhibition with that of a known aromatase inhibitor, fish were also exposed to fadrozole (20 and 100 µg/L). Fadrozole did not significantly decrease the mRNA expression in embryos or adult <italic>Fundulus</italic>
. However, aromatase enzyme activity was significantly decreased in adult ovary and brain tissues. These studies provide a greater molecular understanding of the mechanisms of action of BaP and its potential to impact reproduction or development.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8500246</journal-id>
<journal-id journal-id-type="pubmed-jr-id">21488</journal-id>
<journal-id journal-id-type="nlm-ta">Aquat Toxicol</journal-id>
<journal-title>Aquatic toxicology (Amsterdam, Netherlands)</journal-title>
<issn pub-type="ppub">0166-445X</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">18571745</article-id>
<article-id pub-id-type="pmc">2530897</article-id>
<article-id pub-id-type="manuscript">NIHMS63869</article-id>
<article-id pub-id-type="doi">10.1016/j.aquatox.2008.05.006</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>BENZO(A)PYRENE DECREASES BRAIN AND OVARIAN AROMATASE mRNA EXPRESSION IN <italic>FUNDULUS HETEROCLITUS</italic>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Dong</surname>
<given-names>Wu</given-names>
</name>
<xref ref-type="aff" rid="A1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Lu</given-names>
</name>
<xref ref-type="aff" rid="A1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Thornton</surname>
<given-names>Cammi</given-names>
</name>
<xref ref-type="aff" rid="A1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Scheffler</surname>
<given-names>Brian E.</given-names>
</name>
<xref ref-type="aff" rid="A2">†</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Willett</surname>
<given-names>Kristine L.</given-names>
</name>
<xref ref-type="aff" rid="A1">*</xref>
<xref ref-type="corresp" rid="cor1">1</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>*</label>
Department of Pharmacology and Environmental Toxicology Research Program, School of Pharmacy, University of Mississippi, 38677</aff>
<aff id="A2"><label>†</label>
USDA-ARS-CGRU MSA Genomics Laboratory, 141 Experiment Station Rd., Stoneville, Mississippi 38776</aff>
<author-notes><corresp id="cor1"><label>1</label>
To whom correspondence should be addressed: Department of Pharmacology and Environmental Toxicology Research Program, School of Pharmacy, The University of Mississippi, 315 Faser Hall, Box 1848, University, MS 38677. PH: 662-915-6691. FX: 662-915-5148. E-mail: <email>kwillett@olemiss.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>4</day>
<month>8</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="epub"><day>15</day>
<month>5</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="ppub"><day>30</day>
<month>7</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>30</day>
<month>7</month>
<year>2009</year>
</pub-date>
<volume>88</volume>
<issue>4</issue>
<fpage>289</fpage>
<lpage>300</lpage>
<abstract><p id="P1">The higher molecular weight polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BaP) are typically associated with genotoxicity, however, newer evidence suggests that these compounds may also act as endocrine system disruptors. We hypothesized that altered expression of the P450 enzyme aromatase genes could be a target for reproductive or developmental dysfunction caused by BaP exposure. Aromatase is at least partially responsible for estrogen homeostasis by converting androgens into estrogens. In fish, there are two isoforms of aromatase, a predominantly ovarian form, CYP19A1, and a brain form, CYP19A2. CYP19 mRNA expression was measured following BaP exposure (0, 10, 100 µg/L waterborne for 10 or 15 days) in <italic>Fundulus</italic>
adults, juveniles and embryos by <italic>in situ</italic>
hybridization. The CYP19A1 expression was significantly decreased after BaP exposure in the 3 month old <italic>Fundulus</italic>
immature oocytes, but BaP did not affect CYP19A1 expression at any stage in adult oocytes. In embryo brains, BaP significantly decreased CYP19A2 compared to controls by 3.6-fold at 14 days post-fertilization. In adults, CYP19A2 expression was decreased significantly in the pituitary and hypothalamus (81% and 85% of controls, respectively). Promoter regions of <italic>Fundulus</italic>
CYP19s were cloned, and putative response elements in the CYP19A1 and CYP19A2 promoters such as CRE, AhR and ERE may be involved in BaP-mediated changes in CYP19 expression. In order to compare the mechanism of BaP-mediated inhibition with that of a known aromatase inhibitor, fish were also exposed to fadrozole (20 and 100 µg/L). Fadrozole did not significantly decrease the mRNA expression in embryos or adult <italic>Fundulus</italic>
. However, aromatase enzyme activity was significantly decreased in adult ovary and brain tissues. These studies provide a greater molecular understanding of the mechanisms of action of BaP and its potential to impact reproduction or development.</p>
</abstract>
<kwd-group><kwd>Benzo(a)pyrene</kwd>
<kwd><italic>Fundulus</italic>
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<kwd>Aromatase</kwd>
<kwd>CYP19</kwd>
</kwd-group>
<contract-num rid="ES1">R01 ES012710-01A1</contract-num>
<contract-sponsor id="ES1">National Institute of Environmental Health Sciences : NIEHS</contract-sponsor>
</article-meta>
</front>
</pmc>
</record>
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