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Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin/leptin signaling in female rats
Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by lepti...
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Published in: | Toxicology and applied pharmacology 2017-03, Vol.319, p.22-38 |
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creator | Sena, Gabriela C. Freitas-Lima, Leandro C. Merlo, Eduardo Podratz, Priscila L. de Araújo, Julia F.P. Brandão, Poliane A.A. Carneiro, Maria T.W.D. Zicker, Marina C. Ferreira, Adaliene V.M. Takiya, Christina M. de Lemos Barbosa, Carolina M. Morales, Marcelo M. Santos-Silva, Ana Paula Miranda-Alves, Leandro Silva, Ian V. Graceli, Jones B. |
description | Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by leptin. However, studies that have investigated the obesogenic TBT effects on the HPG axis are especially rare. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin (Kiss) action. Female Wistar rats were administered vehicle and TBT (100ng/kg/day) for 15days via gavage. We analyzed their effects on the tin serum and ovary accumulation (as biomarker of TBT exposure), estrous cyclicity, surge LH levels, GnRH expression, Kiss action, fertility, testosterone levels, ovarian apoptosis, uterine inflammation, fibrosis, estrogen negative feedback, body weight gain, insulin, leptin, adiponectin levels, as well as the glucose tolerance (GTT) and insulin sensitivity tests (IST). TBT led to increased serum and ovary tin levels, irregular estrous cyclicity, and decreased surge LH levels, GnRH expression and Kiss responsiveness. A strong negative correlation between the serum and ovary tin levels with lower Kiss responsiveness and GnRH mRNA expression was observed in TBT rats. An increase in the testosterone levels, ovarian and uterine fibrosis, ovarian apoptosis, and uterine inflammation and a decrease in fertility and estrogen negative feedback were demonstrated in the TBT rats. We also identified an increase in the body weight gain and abnormal GTT and IST tests, which were associated with hyperinsulinemia, hyperleptinemia and hypoadiponectinemia, in the TBT rats. TBT disrupted proper functioning of the HPG axis as a result of abnormal Kiss action. The metabolic dysfunctions co-occur with the HPG axis abnormalities. Hyperleptinemia as a result of obesity induced by TBT may be associated with abnormal HPG function. A strong negative correlation between the hyperleptinemia and lower Kiss responsiveness was observed in the TBT rats. These findings provide evidence that TBT leads to toxic effects direct on the HPG axis and/or indirectly by abnormal metabolic regulation of the HPG axis.
•TBT disrupted proper functioning of the HPG axis in female rats.•TBT leads to obesity and abnormal kisspeptin/leptin signaling in female rats.•TBT impairs GnRH neurons function, estrogen |
doi_str_mv | 10.1016/j.taap.2017.01.021 |
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•TBT disrupted proper functioning of the HPG axis in female rats.•TBT leads to obesity and abnormal kisspeptin/leptin signaling in female rats.•TBT impairs GnRH neurons function, estrogen negative feedback role and fertility in female rats.•TBT leads to hyperleptinemia that may be associated at least in part with abnormal HPG function</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2017.01.021</identifier><identifier>PMID: 28161095</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Animals ; APOPTOSIS ; BIOLOGICAL MARKERS ; Endocrine Disruptors - toxicity ; Endocrine-disrupting chemicals ; Environmental Exposure - adverse effects ; ESTROGENS ; Estrous Cycle - drug effects ; Estrous Cycle - metabolism ; Female ; FERTILITY ; FIBROSIS ; GLUCOSE ; HPG axis ; Hypothalamic Hormones - antagonists & inhibitors ; Hypothalamic Hormones - metabolism ; Hypothalamo-Hypophyseal System - drug effects ; Hypothalamo-Hypophyseal System - metabolism ; HYPOTHALAMUS ; INFLAMMATION ; INSULIN ; Kisspeptin ; Kisspeptins - antagonists & inhibitors ; Kisspeptins - metabolism ; LEPTIN ; Leptin - antagonists & inhibitors ; Leptin - metabolism ; MESSENGER-RNA ; METABOLIC DISEASES ; NERVE CELLS ; Obesity ; Obesity - chemically induced ; Obesity - metabolism ; OVARIES ; Pituitary-Adrenal System - drug effects ; Pituitary-Adrenal System - metabolism ; RATS ; Rats, Wistar ; Reproduction - drug effects ; Reproduction - physiology ; Signal Transduction - drug effects ; Signal Transduction - physiology ; TESTOSTERONE ; TIN ; Trialkyltin Compounds - toxicity ; Tributyltin chloride</subject><ispartof>Toxicology and applied pharmacology, 2017-03, Vol.319, p.22-38</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-ba004c942f7a408bd47a072380333736876abeb5772e02c5d5a5e0fc21dc8b613</citedby><cites>FETCH-LOGICAL-c384t-ba004c942f7a408bd47a072380333736876abeb5772e02c5d5a5e0fc21dc8b613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28161095$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22690939$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Sena, Gabriela C.</creatorcontrib><creatorcontrib>Freitas-Lima, Leandro C.</creatorcontrib><creatorcontrib>Merlo, Eduardo</creatorcontrib><creatorcontrib>Podratz, Priscila L.</creatorcontrib><creatorcontrib>de Araújo, Julia F.P.</creatorcontrib><creatorcontrib>Brandão, Poliane A.A.</creatorcontrib><creatorcontrib>Carneiro, Maria T.W.D.</creatorcontrib><creatorcontrib>Zicker, Marina C.</creatorcontrib><creatorcontrib>Ferreira, Adaliene V.M.</creatorcontrib><creatorcontrib>Takiya, Christina M.</creatorcontrib><creatorcontrib>de Lemos Barbosa, Carolina M.</creatorcontrib><creatorcontrib>Morales, Marcelo M.</creatorcontrib><creatorcontrib>Santos-Silva, Ana Paula</creatorcontrib><creatorcontrib>Miranda-Alves, Leandro</creatorcontrib><creatorcontrib>Silva, Ian V.</creatorcontrib><creatorcontrib>Graceli, Jones B.</creatorcontrib><title>Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin/leptin signaling in female rats</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by leptin. However, studies that have investigated the obesogenic TBT effects on the HPG axis are especially rare. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin (Kiss) action. Female Wistar rats were administered vehicle and TBT (100ng/kg/day) for 15days via gavage. We analyzed their effects on the tin serum and ovary accumulation (as biomarker of TBT exposure), estrous cyclicity, surge LH levels, GnRH expression, Kiss action, fertility, testosterone levels, ovarian apoptosis, uterine inflammation, fibrosis, estrogen negative feedback, body weight gain, insulin, leptin, adiponectin levels, as well as the glucose tolerance (GTT) and insulin sensitivity tests (IST). TBT led to increased serum and ovary tin levels, irregular estrous cyclicity, and decreased surge LH levels, GnRH expression and Kiss responsiveness. A strong negative correlation between the serum and ovary tin levels with lower Kiss responsiveness and GnRH mRNA expression was observed in TBT rats. An increase in the testosterone levels, ovarian and uterine fibrosis, ovarian apoptosis, and uterine inflammation and a decrease in fertility and estrogen negative feedback were demonstrated in the TBT rats. We also identified an increase in the body weight gain and abnormal GTT and IST tests, which were associated with hyperinsulinemia, hyperleptinemia and hypoadiponectinemia, in the TBT rats. TBT disrupted proper functioning of the HPG axis as a result of abnormal Kiss action. The metabolic dysfunctions co-occur with the HPG axis abnormalities. Hyperleptinemia as a result of obesity induced by TBT may be associated with abnormal HPG function. A strong negative correlation between the hyperleptinemia and lower Kiss responsiveness was observed in the TBT rats. These findings provide evidence that TBT leads to toxic effects direct on the HPG axis and/or indirectly by abnormal metabolic regulation of the HPG axis.
•TBT disrupted proper functioning of the HPG axis in female rats.•TBT leads to obesity and abnormal kisspeptin/leptin signaling in female rats.•TBT impairs GnRH neurons function, estrogen negative feedback role and fertility in female rats.•TBT leads to hyperleptinemia that may be associated at least in part with abnormal HPG function</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Animals</subject><subject>APOPTOSIS</subject><subject>BIOLOGICAL MARKERS</subject><subject>Endocrine Disruptors - toxicity</subject><subject>Endocrine-disrupting chemicals</subject><subject>Environmental Exposure - adverse effects</subject><subject>ESTROGENS</subject><subject>Estrous Cycle - drug effects</subject><subject>Estrous Cycle - metabolism</subject><subject>Female</subject><subject>FERTILITY</subject><subject>FIBROSIS</subject><subject>GLUCOSE</subject><subject>HPG axis</subject><subject>Hypothalamic Hormones - antagonists & inhibitors</subject><subject>Hypothalamic Hormones - metabolism</subject><subject>Hypothalamo-Hypophyseal System - drug effects</subject><subject>Hypothalamo-Hypophyseal System - metabolism</subject><subject>HYPOTHALAMUS</subject><subject>INFLAMMATION</subject><subject>INSULIN</subject><subject>Kisspeptin</subject><subject>Kisspeptins - antagonists & inhibitors</subject><subject>Kisspeptins - metabolism</subject><subject>LEPTIN</subject><subject>Leptin - antagonists & inhibitors</subject><subject>Leptin - metabolism</subject><subject>MESSENGER-RNA</subject><subject>METABOLIC DISEASES</subject><subject>NERVE CELLS</subject><subject>Obesity</subject><subject>Obesity - chemically induced</subject><subject>Obesity - metabolism</subject><subject>OVARIES</subject><subject>Pituitary-Adrenal System - drug effects</subject><subject>Pituitary-Adrenal System - metabolism</subject><subject>RATS</subject><subject>Rats, Wistar</subject><subject>Reproduction - drug effects</subject><subject>Reproduction - physiology</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - physiology</subject><subject>TESTOSTERONE</subject><subject>TIN</subject><subject>Trialkyltin Compounds - toxicity</subject><subject>Tributyltin chloride</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp9UclqHDEQFSEhntj5gRyCIOdul9Q75BKMs4DBFwd8E1qqZzTplhpJbTI_lO-M2pPkmFNR1Ft49Qh5x6BkwNrrY5mkXEoOrCuBlcDZC7JjMLQFVFX1kuwAalYA9I8X5E2MRwAY6pq9Jhe8Z20GNjvy69Y92eDdjC7JiXqF0e_R0RSsWtNpStZRfZh8sAbphNJEmjyVyvkwZ_zhtPh0kJOcrS4Wm1abZDgVe--kyWf500Y6rk4n6x1VJ2psDOvyvGXhHzbGBfPqrqfnQaPdOzlZt9_OI2YLpEGmeEVejXKK-PbPvCTfP98-3Hwt7u6_fLv5dFfoqq9ToWSOrIeaj52soVem7iR0vOq3h3RV23etVKiaruMIXDemkQ3CqDkzulctqy7Jh7Ouj8mKqG1CfdDeOdRJcN4OMFRDRvEzSgcfY8BRLMHOObhgILZqxFFs1YitGgFM5Goy6f2ZtKxqRvOP8reLDPh4BmAO-GQxbP7oNBobNnvj7f_0fwP4Z6TI</recordid><startdate>20170315</startdate><enddate>20170315</enddate><creator>Sena, Gabriela C.</creator><creator>Freitas-Lima, Leandro C.</creator><creator>Merlo, Eduardo</creator><creator>Podratz, Priscila L.</creator><creator>de Araújo, Julia F.P.</creator><creator>Brandão, Poliane A.A.</creator><creator>Carneiro, Maria T.W.D.</creator><creator>Zicker, Marina C.</creator><creator>Ferreira, Adaliene V.M.</creator><creator>Takiya, Christina M.</creator><creator>de Lemos Barbosa, Carolina M.</creator><creator>Morales, Marcelo M.</creator><creator>Santos-Silva, Ana Paula</creator><creator>Miranda-Alves, Leandro</creator><creator>Silva, Ian V.</creator><creator>Graceli, Jones B.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>OTOTI</scope></search><sort><creationdate>20170315</creationdate><title>Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin/leptin signaling in female rats</title><author>Sena, Gabriela C. ; Freitas-Lima, Leandro C. ; Merlo, Eduardo ; Podratz, Priscila L. ; de Araújo, Julia F.P. ; Brandão, Poliane A.A. ; Carneiro, Maria T.W.D. ; Zicker, Marina C. ; Ferreira, Adaliene V.M. ; Takiya, Christina M. ; de Lemos Barbosa, Carolina M. ; Morales, Marcelo M. ; Santos-Silva, Ana Paula ; Miranda-Alves, Leandro ; Silva, Ian V. ; Graceli, Jones B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-ba004c942f7a408bd47a072380333736876abeb5772e02c5d5a5e0fc21dc8b613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>Animals</topic><topic>APOPTOSIS</topic><topic>BIOLOGICAL MARKERS</topic><topic>Endocrine Disruptors - toxicity</topic><topic>Endocrine-disrupting chemicals</topic><topic>Environmental Exposure - adverse effects</topic><topic>ESTROGENS</topic><topic>Estrous Cycle - drug effects</topic><topic>Estrous Cycle - metabolism</topic><topic>Female</topic><topic>FERTILITY</topic><topic>FIBROSIS</topic><topic>GLUCOSE</topic><topic>HPG axis</topic><topic>Hypothalamic Hormones - antagonists & inhibitors</topic><topic>Hypothalamic Hormones - metabolism</topic><topic>Hypothalamo-Hypophyseal System - drug effects</topic><topic>Hypothalamo-Hypophyseal System - metabolism</topic><topic>HYPOTHALAMUS</topic><topic>INFLAMMATION</topic><topic>INSULIN</topic><topic>Kisspeptin</topic><topic>Kisspeptins - antagonists & inhibitors</topic><topic>Kisspeptins - metabolism</topic><topic>LEPTIN</topic><topic>Leptin - antagonists & inhibitors</topic><topic>Leptin - metabolism</topic><topic>MESSENGER-RNA</topic><topic>METABOLIC DISEASES</topic><topic>NERVE CELLS</topic><topic>Obesity</topic><topic>Obesity - chemically induced</topic><topic>Obesity - metabolism</topic><topic>OVARIES</topic><topic>Pituitary-Adrenal System - drug effects</topic><topic>Pituitary-Adrenal System - metabolism</topic><topic>RATS</topic><topic>Rats, Wistar</topic><topic>Reproduction - drug effects</topic><topic>Reproduction - physiology</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - physiology</topic><topic>TESTOSTERONE</topic><topic>TIN</topic><topic>Trialkyltin Compounds - toxicity</topic><topic>Tributyltin chloride</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sena, Gabriela C.</creatorcontrib><creatorcontrib>Freitas-Lima, Leandro C.</creatorcontrib><creatorcontrib>Merlo, Eduardo</creatorcontrib><creatorcontrib>Podratz, Priscila L.</creatorcontrib><creatorcontrib>de Araújo, Julia F.P.</creatorcontrib><creatorcontrib>Brandão, Poliane A.A.</creatorcontrib><creatorcontrib>Carneiro, Maria T.W.D.</creatorcontrib><creatorcontrib>Zicker, Marina C.</creatorcontrib><creatorcontrib>Ferreira, Adaliene V.M.</creatorcontrib><creatorcontrib>Takiya, Christina M.</creatorcontrib><creatorcontrib>de Lemos Barbosa, Carolina M.</creatorcontrib><creatorcontrib>Morales, Marcelo M.</creatorcontrib><creatorcontrib>Santos-Silva, Ana Paula</creatorcontrib><creatorcontrib>Miranda-Alves, Leandro</creatorcontrib><creatorcontrib>Silva, Ian V.</creatorcontrib><creatorcontrib>Graceli, Jones B.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>OSTI.GOV</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sena, Gabriela C.</au><au>Freitas-Lima, Leandro C.</au><au>Merlo, Eduardo</au><au>Podratz, Priscila L.</au><au>de Araújo, Julia F.P.</au><au>Brandão, Poliane A.A.</au><au>Carneiro, Maria T.W.D.</au><au>Zicker, Marina C.</au><au>Ferreira, Adaliene V.M.</au><au>Takiya, Christina M.</au><au>de Lemos Barbosa, Carolina M.</au><au>Morales, Marcelo M.</au><au>Santos-Silva, Ana Paula</au><au>Miranda-Alves, Leandro</au><au>Silva, Ian V.</au><au>Graceli, Jones B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin/leptin signaling in female rats</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2017-03-15</date><risdate>2017</risdate><volume>319</volume><spage>22</spage><epage>38</epage><pages>22-38</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><abstract>Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by leptin. However, studies that have investigated the obesogenic TBT effects on the HPG axis are especially rare. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin (Kiss) action. Female Wistar rats were administered vehicle and TBT (100ng/kg/day) for 15days via gavage. We analyzed their effects on the tin serum and ovary accumulation (as biomarker of TBT exposure), estrous cyclicity, surge LH levels, GnRH expression, Kiss action, fertility, testosterone levels, ovarian apoptosis, uterine inflammation, fibrosis, estrogen negative feedback, body weight gain, insulin, leptin, adiponectin levels, as well as the glucose tolerance (GTT) and insulin sensitivity tests (IST). TBT led to increased serum and ovary tin levels, irregular estrous cyclicity, and decreased surge LH levels, GnRH expression and Kiss responsiveness. A strong negative correlation between the serum and ovary tin levels with lower Kiss responsiveness and GnRH mRNA expression was observed in TBT rats. An increase in the testosterone levels, ovarian and uterine fibrosis, ovarian apoptosis, and uterine inflammation and a decrease in fertility and estrogen negative feedback were demonstrated in the TBT rats. We also identified an increase in the body weight gain and abnormal GTT and IST tests, which were associated with hyperinsulinemia, hyperleptinemia and hypoadiponectinemia, in the TBT rats. TBT disrupted proper functioning of the HPG axis as a result of abnormal Kiss action. The metabolic dysfunctions co-occur with the HPG axis abnormalities. Hyperleptinemia as a result of obesity induced by TBT may be associated with abnormal HPG function. A strong negative correlation between the hyperleptinemia and lower Kiss responsiveness was observed in the TBT rats. These findings provide evidence that TBT leads to toxic effects direct on the HPG axis and/or indirectly by abnormal metabolic regulation of the HPG axis.
•TBT disrupted proper functioning of the HPG axis in female rats.•TBT leads to obesity and abnormal kisspeptin/leptin signaling in female rats.•TBT impairs GnRH neurons function, estrogen negative feedback role and fertility in female rats.•TBT leads to hyperleptinemia that may be associated at least in part with abnormal HPG function</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28161095</pmid><doi>10.1016/j.taap.2017.01.021</doi><tpages>17</tpages></addata></record> |
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subjects | 60 APPLIED LIFE SCIENCES Animals APOPTOSIS BIOLOGICAL MARKERS Endocrine Disruptors - toxicity Endocrine-disrupting chemicals Environmental Exposure - adverse effects ESTROGENS Estrous Cycle - drug effects Estrous Cycle - metabolism Female FERTILITY FIBROSIS GLUCOSE HPG axis Hypothalamic Hormones - antagonists & inhibitors Hypothalamic Hormones - metabolism Hypothalamo-Hypophyseal System - drug effects Hypothalamo-Hypophyseal System - metabolism HYPOTHALAMUS INFLAMMATION INSULIN Kisspeptin Kisspeptins - antagonists & inhibitors Kisspeptins - metabolism LEPTIN Leptin - antagonists & inhibitors Leptin - metabolism MESSENGER-RNA METABOLIC DISEASES NERVE CELLS Obesity Obesity - chemically induced Obesity - metabolism OVARIES Pituitary-Adrenal System - drug effects Pituitary-Adrenal System - metabolism RATS Rats, Wistar Reproduction - drug effects Reproduction - physiology Signal Transduction - drug effects Signal Transduction - physiology TESTOSTERONE TIN Trialkyltin Compounds - toxicity Tributyltin chloride |
title | Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin/leptin signaling in female rats |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T14%3A58%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-elsevier_osti_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Environmental%20obesogen%20tributyltin%20chloride%20leads%20to%20abnormal%20hypothalamic-pituitary-gonadal%20axis%20function%20by%20disruption%20in%20kisspeptin/leptin%20signaling%20in%20female%20rats&rft.jtitle=Toxicology%20and%20applied%20pharmacology&rft.au=Sena,%20Gabriela%20C.&rft.date=2017-03-15&rft.volume=319&rft.spage=22&rft.epage=38&rft.pages=22-38&rft.issn=0041-008X&rft.eissn=1096-0333&rft_id=info:doi/10.1016/j.taap.2017.01.021&rft_dat=%3Celsevier_osti_%3ES0041008X17300492%3C/elsevier_osti_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c384t-ba004c942f7a408bd47a072380333736876abeb5772e02c5d5a5e0fc21dc8b613%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/28161095&rfr_iscdi=true |