Increased Hepatobiliary Clearance of Unconjugated Thyroxine Determines DMP 904-Induced Alterations in Thyroid Hormone Homeostasis in Rats
4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine (DMP 904) is a potent and selective antagonist of corticotropin releasing factor receptor-1 (CRF1 receptor) with an efficacious anxiolytic profile in preclinical animal models. In subchronic toxicity studies in S...
Gespeichert in:
| Veröffentlicht in: | Toxicological sciences 2005-04, Vol.84 (2), p.232-242 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 242 |
|---|---|
| container_issue | 2 |
| container_start_page | 232 |
| container_title | Toxicological sciences |
| container_volume | 84 |
| creator | Wong, Harvey Lehman-McKeeman, Lois D. Grubb, Mary F. Grossman, Scott J. Bhaskaran, Vasanthi M. Solon, Eric G. Shen, Helen S. L. Gerson, Ronald J. Car, Bruce D. Zhao, Bitao Gemzik, Brian |
| description | 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine (DMP 904) is a potent and selective antagonist of corticotropin releasing factor receptor-1 (CRF1 receptor) with an efficacious anxiolytic profile in preclinical animal models. In subchronic toxicity studies in Sprague-Dawley rats, DMP 904 produced thyroid follicular cell hypertrophy and hyperplasia, and a low incidence of follicular cell adenoma. The current investigations were designed to determine the mode of action by which DMP 904 disrupts thyroid homeostasis in male rats. Five-day treatment with DMP 904 (300 mg/kg/day) dramatically lowered serum thyroxine (T4) to levels below detectable limits ( |
| doi_str_mv | 10.1093/toxsci/kfi094 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_17781454</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17781454</sourcerecordid><originalsourceid>FETCH-LOGICAL-c399t-de65e725070b139aa03dce598cbec206b6b635f7364feaadbb651fb1a7d312f53</originalsourceid><addsrcrecordid>eNpFkMFO3DAURS3UCih0yRZl1V3AHsfOeImGwoxE1YKAVmysF-cFDIk9tR1p-IT-dd1mBPLCT77nXUuHkCNGTxhV_DT5TTT29KWzVFU7ZD8_ypKqmfqwnSWd0z3yKcZnShmTVO2SPSZkzeeV3Cd_Vs4EhIhtscQ1JN_Y3kJ4LRY9QgBnsPBdceeMd8_jI6TM3T69Br-xDotzTBiGPMXi_NuPQtGqXLl2NBk663MEyXoXC-umHZv_8GHweXPpB_QxQbT_4xtI8ZB87KCP-Hl7H5C7i6-3i2V59f1ytTi7Kg1XKpUtSoH1TNCaNowrAMpbg0LNTYNmRmWTDxddzWXVIUDbNFKwrmFQt5zNOsEPyJepdx387xFj0oONBvseHPoxalbXc1aJKoPlBJrgYwzY6XWwQ3ajGdX_3OvJvZ7cZ_54Wzw2A7bv9Fb2e6GNCTdvOYQXnYla6OWvB82uf7Lq5v5S3_O_qiqT_w</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17781454</pqid></control><display><type>article</type><title>Increased Hepatobiliary Clearance of Unconjugated Thyroxine Determines DMP 904-Induced Alterations in Thyroid Hormone Homeostasis in Rats</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Wong, Harvey ; Lehman-McKeeman, Lois D. ; Grubb, Mary F. ; Grossman, Scott J. ; Bhaskaran, Vasanthi M. ; Solon, Eric G. ; Shen, Helen S. L. ; Gerson, Ronald J. ; Car, Bruce D. ; Zhao, Bitao ; Gemzik, Brian</creator><creatorcontrib>Wong, Harvey ; Lehman-McKeeman, Lois D. ; Grubb, Mary F. ; Grossman, Scott J. ; Bhaskaran, Vasanthi M. ; Solon, Eric G. ; Shen, Helen S. L. ; Gerson, Ronald J. ; Car, Bruce D. ; Zhao, Bitao ; Gemzik, Brian</creatorcontrib><description>4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine (DMP 904) is a potent and selective antagonist of corticotropin releasing factor receptor-1 (CRF1 receptor) with an efficacious anxiolytic profile in preclinical animal models. In subchronic toxicity studies in Sprague-Dawley rats, DMP 904 produced thyroid follicular cell hypertrophy and hyperplasia, and a low incidence of follicular cell adenoma. The current investigations were designed to determine the mode of action by which DMP 904 disrupts thyroid homeostasis in male rats. Five-day treatment with DMP 904 (300 mg/kg/day) dramatically lowered serum thyroxine (T4) to levels below detectable limits (<1 μg/dl) by 72 h, with concurrent decreases in triiodothyronine (T3, about a 70% decrease) and increases in thyroid stimulating hormone (TSH; about a three-fold increase). DMP 904 increased [125I]T4 total body clearance (Cltb) (38.21 ± 10.45 ml/h) compared to control (5.61 ± 0.59 ml/h) and phenobarbital-treated rats (7.92 ± 1.62 ml/h). This increase in Cltb was associated with a significant increase in biliary clearance (Clbile) of unconjugated [125I]T4 (nearly 80-times control rates) and increased liver:blood ratios of T4, suggestive of enhanced hepatic uptake of T4. A single dose of DMP 904 (200 mg/kg) increased mRNA levels of hepatic cytochrome P450s (CYP 3A1 and CYP 2B1) and UDP-glucuronosyltransferases (UGT 1A1 and UGT 1A2). DMP 904 also induced mRNAs of the canalicular transporter, multi-drug resistance protein-2 (Mrp2) and sinusoidal transporters, organic anion transporting proteins (Oatp1 and Oatp2) within 24 h. Western blot analysis confirmed DMP 904 related increases in Oatp2 protein expression. Collectively, these data suggest that DMP 904 is an agonist of the constitutive androstane receptor (CAR) and pregnane X receptor (PXR) and that the decreased serum levels of T4 and T3 resulted from increased hepatobiliary clearance. However, DMP 904 is distinguished from other compounds associated with similar effects on thyroid hormone homeostasis because its effects were primarily related to increased biliary excretion of unconjugated T4.</description><identifier>ISSN: 1096-6080</identifier><identifier>EISSN: 1096-0929</identifier><identifier>DOI: 10.1093/toxsci/kfi094</identifier><identifier>PMID: 15673846</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Administration, Oral ; Animals ; Autoradiography ; Bile - metabolism ; biliary clearance ; Corticotropin-Releasing Hormone - antagonists & inhibitors ; Cytochrome P-450 Enzyme System - genetics ; Cytochrome P-450 Enzyme System - metabolism ; Glucuronosyltransferase - genetics ; Glucuronosyltransferase - metabolism ; hepatic transporters ; Homeostasis - drug effects ; Liver - drug effects ; Liver - metabolism ; Male ; Oatp2 ; Organic Anion Transporters ; Organic Cation Transport Proteins - metabolism ; Pyrazoles - toxicity ; Pyrimidines - toxicity ; rat ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - metabolism ; Thyroid Gland - drug effects ; Thyroid Gland - metabolism ; thyroid stimulating hormone ; Thyrotropin - blood ; thyroxine ; Thyroxine - blood ; triiodothyronine ; Triiodothyronine - metabolism</subject><ispartof>Toxicological sciences, 2005-04, Vol.84 (2), p.232-242</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-de65e725070b139aa03dce598cbec206b6b635f7364feaadbb651fb1a7d312f53</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15673846$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wong, Harvey</creatorcontrib><creatorcontrib>Lehman-McKeeman, Lois D.</creatorcontrib><creatorcontrib>Grubb, Mary F.</creatorcontrib><creatorcontrib>Grossman, Scott J.</creatorcontrib><creatorcontrib>Bhaskaran, Vasanthi M.</creatorcontrib><creatorcontrib>Solon, Eric G.</creatorcontrib><creatorcontrib>Shen, Helen S. L.</creatorcontrib><creatorcontrib>Gerson, Ronald J.</creatorcontrib><creatorcontrib>Car, Bruce D.</creatorcontrib><creatorcontrib>Zhao, Bitao</creatorcontrib><creatorcontrib>Gemzik, Brian</creatorcontrib><title>Increased Hepatobiliary Clearance of Unconjugated Thyroxine Determines DMP 904-Induced Alterations in Thyroid Hormone Homeostasis in Rats</title><title>Toxicological sciences</title><addtitle>Toxicol. Sci</addtitle><description>4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine (DMP 904) is a potent and selective antagonist of corticotropin releasing factor receptor-1 (CRF1 receptor) with an efficacious anxiolytic profile in preclinical animal models. In subchronic toxicity studies in Sprague-Dawley rats, DMP 904 produced thyroid follicular cell hypertrophy and hyperplasia, and a low incidence of follicular cell adenoma. The current investigations were designed to determine the mode of action by which DMP 904 disrupts thyroid homeostasis in male rats. Five-day treatment with DMP 904 (300 mg/kg/day) dramatically lowered serum thyroxine (T4) to levels below detectable limits (<1 μg/dl) by 72 h, with concurrent decreases in triiodothyronine (T3, about a 70% decrease) and increases in thyroid stimulating hormone (TSH; about a three-fold increase). DMP 904 increased [125I]T4 total body clearance (Cltb) (38.21 ± 10.45 ml/h) compared to control (5.61 ± 0.59 ml/h) and phenobarbital-treated rats (7.92 ± 1.62 ml/h). This increase in Cltb was associated with a significant increase in biliary clearance (Clbile) of unconjugated [125I]T4 (nearly 80-times control rates) and increased liver:blood ratios of T4, suggestive of enhanced hepatic uptake of T4. A single dose of DMP 904 (200 mg/kg) increased mRNA levels of hepatic cytochrome P450s (CYP 3A1 and CYP 2B1) and UDP-glucuronosyltransferases (UGT 1A1 and UGT 1A2). DMP 904 also induced mRNAs of the canalicular transporter, multi-drug resistance protein-2 (Mrp2) and sinusoidal transporters, organic anion transporting proteins (Oatp1 and Oatp2) within 24 h. Western blot analysis confirmed DMP 904 related increases in Oatp2 protein expression. Collectively, these data suggest that DMP 904 is an agonist of the constitutive androstane receptor (CAR) and pregnane X receptor (PXR) and that the decreased serum levels of T4 and T3 resulted from increased hepatobiliary clearance. However, DMP 904 is distinguished from other compounds associated with similar effects on thyroid hormone homeostasis because its effects were primarily related to increased biliary excretion of unconjugated T4.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Autoradiography</subject><subject>Bile - metabolism</subject><subject>biliary clearance</subject><subject>Corticotropin-Releasing Hormone - antagonists & inhibitors</subject><subject>Cytochrome P-450 Enzyme System - genetics</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Glucuronosyltransferase - genetics</subject><subject>Glucuronosyltransferase - metabolism</subject><subject>hepatic transporters</subject><subject>Homeostasis - drug effects</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Oatp2</subject><subject>Organic Anion Transporters</subject><subject>Organic Cation Transport Proteins - metabolism</subject><subject>Pyrazoles - toxicity</subject><subject>Pyrimidines - toxicity</subject><subject>rat</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - metabolism</subject><subject>Thyroid Gland - drug effects</subject><subject>Thyroid Gland - metabolism</subject><subject>thyroid stimulating hormone</subject><subject>Thyrotropin - blood</subject><subject>thyroxine</subject><subject>Thyroxine - blood</subject><subject>triiodothyronine</subject><subject>Triiodothyronine - metabolism</subject><issn>1096-6080</issn><issn>1096-0929</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMFO3DAURS3UCih0yRZl1V3AHsfOeImGwoxE1YKAVmysF-cFDIk9tR1p-IT-dd1mBPLCT77nXUuHkCNGTxhV_DT5TTT29KWzVFU7ZD8_ypKqmfqwnSWd0z3yKcZnShmTVO2SPSZkzeeV3Cd_Vs4EhIhtscQ1JN_Y3kJ4LRY9QgBnsPBdceeMd8_jI6TM3T69Br-xDotzTBiGPMXi_NuPQtGqXLl2NBk663MEyXoXC-umHZv_8GHweXPpB_QxQbT_4xtI8ZB87KCP-Hl7H5C7i6-3i2V59f1ytTi7Kg1XKpUtSoH1TNCaNowrAMpbg0LNTYNmRmWTDxddzWXVIUDbNFKwrmFQt5zNOsEPyJepdx387xFj0oONBvseHPoxalbXc1aJKoPlBJrgYwzY6XWwQ3ajGdX_3OvJvZ7cZ_54Wzw2A7bv9Fb2e6GNCTdvOYQXnYla6OWvB82uf7Lq5v5S3_O_qiqT_w</recordid><startdate>20050401</startdate><enddate>20050401</enddate><creator>Wong, Harvey</creator><creator>Lehman-McKeeman, Lois D.</creator><creator>Grubb, Mary F.</creator><creator>Grossman, Scott J.</creator><creator>Bhaskaran, Vasanthi M.</creator><creator>Solon, Eric G.</creator><creator>Shen, Helen S. L.</creator><creator>Gerson, Ronald J.</creator><creator>Car, Bruce D.</creator><creator>Zhao, Bitao</creator><creator>Gemzik, Brian</creator><general>Oxford University Press</general><scope>BSCLL</scope><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>7U7</scope><scope>C1K</scope></search><sort><creationdate>20050401</creationdate><title>Increased Hepatobiliary Clearance of Unconjugated Thyroxine Determines DMP 904-Induced Alterations in Thyroid Hormone Homeostasis in Rats</title><author>Wong, Harvey ; Lehman-McKeeman, Lois D. ; Grubb, Mary F. ; Grossman, Scott J. ; Bhaskaran, Vasanthi M. ; Solon, Eric G. ; Shen, Helen S. L. ; Gerson, Ronald J. ; Car, Bruce D. ; Zhao, Bitao ; Gemzik, Brian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-de65e725070b139aa03dce598cbec206b6b635f7364feaadbb651fb1a7d312f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Autoradiography</topic><topic>Bile - metabolism</topic><topic>biliary clearance</topic><topic>Corticotropin-Releasing Hormone - antagonists & inhibitors</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Glucuronosyltransferase - genetics</topic><topic>Glucuronosyltransferase - metabolism</topic><topic>hepatic transporters</topic><topic>Homeostasis - drug effects</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Oatp2</topic><topic>Organic Anion Transporters</topic><topic>Organic Cation Transport Proteins - metabolism</topic><topic>Pyrazoles - toxicity</topic><topic>Pyrimidines - toxicity</topic><topic>rat</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - metabolism</topic><topic>Thyroid Gland - drug effects</topic><topic>Thyroid Gland - metabolism</topic><topic>thyroid stimulating hormone</topic><topic>Thyrotropin - blood</topic><topic>thyroxine</topic><topic>Thyroxine - blood</topic><topic>triiodothyronine</topic><topic>Triiodothyronine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wong, Harvey</creatorcontrib><creatorcontrib>Lehman-McKeeman, Lois D.</creatorcontrib><creatorcontrib>Grubb, Mary F.</creatorcontrib><creatorcontrib>Grossman, Scott J.</creatorcontrib><creatorcontrib>Bhaskaran, Vasanthi M.</creatorcontrib><creatorcontrib>Solon, Eric G.</creatorcontrib><creatorcontrib>Shen, Helen S. L.</creatorcontrib><creatorcontrib>Gerson, Ronald J.</creatorcontrib><creatorcontrib>Car, Bruce D.</creatorcontrib><creatorcontrib>Zhao, Bitao</creatorcontrib><creatorcontrib>Gemzik, Brian</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Toxicological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wong, Harvey</au><au>Lehman-McKeeman, Lois D.</au><au>Grubb, Mary F.</au><au>Grossman, Scott J.</au><au>Bhaskaran, Vasanthi M.</au><au>Solon, Eric G.</au><au>Shen, Helen S. L.</au><au>Gerson, Ronald J.</au><au>Car, Bruce D.</au><au>Zhao, Bitao</au><au>Gemzik, Brian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased Hepatobiliary Clearance of Unconjugated Thyroxine Determines DMP 904-Induced Alterations in Thyroid Hormone Homeostasis in Rats</atitle><jtitle>Toxicological sciences</jtitle><addtitle>Toxicol. Sci</addtitle><date>2005-04-01</date><risdate>2005</risdate><volume>84</volume><issue>2</issue><spage>232</spage><epage>242</epage><pages>232-242</pages><issn>1096-6080</issn><eissn>1096-0929</eissn><abstract>4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine (DMP 904) is a potent and selective antagonist of corticotropin releasing factor receptor-1 (CRF1 receptor) with an efficacious anxiolytic profile in preclinical animal models. In subchronic toxicity studies in Sprague-Dawley rats, DMP 904 produced thyroid follicular cell hypertrophy and hyperplasia, and a low incidence of follicular cell adenoma. The current investigations were designed to determine the mode of action by which DMP 904 disrupts thyroid homeostasis in male rats. Five-day treatment with DMP 904 (300 mg/kg/day) dramatically lowered serum thyroxine (T4) to levels below detectable limits (<1 μg/dl) by 72 h, with concurrent decreases in triiodothyronine (T3, about a 70% decrease) and increases in thyroid stimulating hormone (TSH; about a three-fold increase). DMP 904 increased [125I]T4 total body clearance (Cltb) (38.21 ± 10.45 ml/h) compared to control (5.61 ± 0.59 ml/h) and phenobarbital-treated rats (7.92 ± 1.62 ml/h). This increase in Cltb was associated with a significant increase in biliary clearance (Clbile) of unconjugated [125I]T4 (nearly 80-times control rates) and increased liver:blood ratios of T4, suggestive of enhanced hepatic uptake of T4. A single dose of DMP 904 (200 mg/kg) increased mRNA levels of hepatic cytochrome P450s (CYP 3A1 and CYP 2B1) and UDP-glucuronosyltransferases (UGT 1A1 and UGT 1A2). DMP 904 also induced mRNAs of the canalicular transporter, multi-drug resistance protein-2 (Mrp2) and sinusoidal transporters, organic anion transporting proteins (Oatp1 and Oatp2) within 24 h. Western blot analysis confirmed DMP 904 related increases in Oatp2 protein expression. Collectively, these data suggest that DMP 904 is an agonist of the constitutive androstane receptor (CAR) and pregnane X receptor (PXR) and that the decreased serum levels of T4 and T3 resulted from increased hepatobiliary clearance. However, DMP 904 is distinguished from other compounds associated with similar effects on thyroid hormone homeostasis because its effects were primarily related to increased biliary excretion of unconjugated T4.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>15673846</pmid><doi>10.1093/toxsci/kfi094</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1096-6080 |
| ispartof | Toxicological sciences, 2005-04, Vol.84 (2), p.232-242 |
| issn | 1096-6080 1096-0929 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_17781454 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Administration, Oral Animals Autoradiography Bile - metabolism biliary clearance Corticotropin-Releasing Hormone - antagonists & inhibitors Cytochrome P-450 Enzyme System - genetics Cytochrome P-450 Enzyme System - metabolism Glucuronosyltransferase - genetics Glucuronosyltransferase - metabolism hepatic transporters Homeostasis - drug effects Liver - drug effects Liver - metabolism Male Oatp2 Organic Anion Transporters Organic Cation Transport Proteins - metabolism Pyrazoles - toxicity Pyrimidines - toxicity rat Rats Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - metabolism Thyroid Gland - drug effects Thyroid Gland - metabolism thyroid stimulating hormone Thyrotropin - blood thyroxine Thyroxine - blood triiodothyronine Triiodothyronine - metabolism |
| title | Increased Hepatobiliary Clearance of Unconjugated Thyroxine Determines DMP 904-Induced Alterations in Thyroid Hormone Homeostasis in Rats |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T03%3A17%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Increased%20Hepatobiliary%20Clearance%20of%20Unconjugated%20Thyroxine%20Determines%20DMP%20904-Induced%20Alterations%20in%20Thyroid%20Hormone%20Homeostasis%20in%20Rats&rft.jtitle=Toxicological%20sciences&rft.au=Wong,%20Harvey&rft.date=2005-04-01&rft.volume=84&rft.issue=2&rft.spage=232&rft.epage=242&rft.pages=232-242&rft.issn=1096-6080&rft.eissn=1096-0929&rft_id=info:doi/10.1093/toxsci/kfi094&rft_dat=%3Cproquest_cross%3E17781454%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=17781454&rft_id=info:pmid/15673846&rfr_iscdi=true |