Analysis of Lysophosphatidic Acid (LPA) Receptor and LPA-Induced Endometrial Prostaglandin-Endoperoxide Synthase 2 Expression in the Porcine Uterus
Lysophosphatidic acid (LPA), a simple phospholipid-derived mediator with diverse biological actions, acts through the specific G protein-coupled receptors endothelial differentiation gene (EDG) 2, EDG4, EDG7, and GPR23. Recent studies indicate a critical role for LPA receptor signaling in embryo imp...
Gespeichert in:
| Veröffentlicht in: | Endocrinology (Philadelphia) 2008-12, Vol.149 (12), p.6166-6175 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 6175 |
|---|---|
| container_issue | 12 |
| container_start_page | 6166 |
| container_title | Endocrinology (Philadelphia) |
| container_volume | 149 |
| creator | Seo, Heewon Kim, Mingoo Choi, Yohan Lee, Chang-Kyu Ka, Hakhyun |
| description | Lysophosphatidic acid (LPA), a simple phospholipid-derived mediator with diverse biological actions, acts through the specific G protein-coupled receptors endothelial differentiation gene (EDG) 2, EDG4, EDG7, and GPR23. Recent studies indicate a critical role for LPA receptor signaling in embryo implantation. To understand how LPA acts in the uterus during pregnancy in pigs, we evaluated: 1) spatial and temporal expression of LPA receptors in the uterine endometrium during the estrous cycle and pregnancy and in early-stage concepti, 2) LPA levels in uterine luminal fluids from d 12 of the estrous cycle and pregnancy, 3) effects of steroid hormones on EDG7 mRNA levels, and 4) effects of LPA on prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA levels in the uterine endometrium using explant cultures. Of the four receptors, EDG7 was dominant, and its expression was regulated by pregnancy stage and status. EDG7 expression was highest on d 12 pregnancy, and localized to the luminal and glandular epithelium, and EDG7 mRNA levels were elevated by estrogen in the endometrium. EDG7 expression was also detected in concepti of d 12 and 15. LPA with various fatty acyl groups was present in the uterine lumen on d 12 of both the estrous cycle and pregnancy. LPA increased PTGS2 mRNA abundance in the uterine endometrium. These results indicate that LPA produced in the uterine endometrium may play a critical role in uterine endometrial function and conceptus development through EDG7-mediated PTGS2 expression during implantation and establishment of pregnancy in pigs. |
| doi_str_mv | 10.1210/en.2008-0354 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69820927</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1210/en.2008-0354</oup_id><sourcerecordid>69820927</sourcerecordid><originalsourceid>FETCH-LOGICAL-c527t-cfd2d50e2816b196ecb5ec231c6f7f20efde1a6f1925100b0b7da916fc833ad3</originalsourceid><addsrcrecordid>eNp1kVtrFDEYhoNY7Lp657UERGvBqTnMKZdL2drCgovW6yGTfHFTZpNpMgPd3-EfNuMOFsRehSQP3-F9EHpDyQVllHwGd8EIqTPCi_wZWlCRF1lFK_IcLQihPKsYq07Ryxjv0jXPc_4CndK6IrxkYoF-rZzsDtFG7A3eHKLvdz72OzlYbRVeKavxx812dY6_gYJ-8AFLp3F6yW6cHhVovHba72EIVnZ4G3wc5M8uMdZl008PwT9YDfj7wQ07GQEzvH7oA8RovcPW4WEHeOuDsg7wjwHCGF-hEyO7CK_nc4lur9a3l9fZ5uuXm8vVJlMFq4ZMGc10QYDVtGypKEG1BSjGqSpNZRgBo4HK0lDBCkpIS9pKS0FLo2rOpeZL9OFYtg_-foQ4NHsbFXRpevBjbEpRMyJYlcB3_4B3fgwpt9hwykkhiEhxLtGnI6VSCDGAafpg9zIcGkqayVQDrplMNZOphL-di47tHvQjPKtJwPsZkFHJzgTplI1_uTQaF7WYuLMj58f-qZbZ3JIfSUhiVEiB__HwuM1_B_0NbHS5uw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3130590970</pqid></control><display><type>article</type><title>Analysis of Lysophosphatidic Acid (LPA) Receptor and LPA-Induced Endometrial Prostaglandin-Endoperoxide Synthase 2 Expression in the Porcine Uterus</title><source>MEDLINE</source><source>Oxford Journals - Connect here FIRST to enable access</source><source>Alma/SFX Local Collection</source><source>EZB Electronic Journals Library</source><creator>Seo, Heewon ; Kim, Mingoo ; Choi, Yohan ; Lee, Chang-Kyu ; Ka, Hakhyun</creator><creatorcontrib>Seo, Heewon ; Kim, Mingoo ; Choi, Yohan ; Lee, Chang-Kyu ; Ka, Hakhyun</creatorcontrib><description>Lysophosphatidic acid (LPA), a simple phospholipid-derived mediator with diverse biological actions, acts through the specific G protein-coupled receptors endothelial differentiation gene (EDG) 2, EDG4, EDG7, and GPR23. Recent studies indicate a critical role for LPA receptor signaling in embryo implantation. To understand how LPA acts in the uterus during pregnancy in pigs, we evaluated: 1) spatial and temporal expression of LPA receptors in the uterine endometrium during the estrous cycle and pregnancy and in early-stage concepti, 2) LPA levels in uterine luminal fluids from d 12 of the estrous cycle and pregnancy, 3) effects of steroid hormones on EDG7 mRNA levels, and 4) effects of LPA on prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA levels in the uterine endometrium using explant cultures. Of the four receptors, EDG7 was dominant, and its expression was regulated by pregnancy stage and status. EDG7 expression was highest on d 12 pregnancy, and localized to the luminal and glandular epithelium, and EDG7 mRNA levels were elevated by estrogen in the endometrium. EDG7 expression was also detected in concepti of d 12 and 15. LPA with various fatty acyl groups was present in the uterine lumen on d 12 of both the estrous cycle and pregnancy. LPA increased PTGS2 mRNA abundance in the uterine endometrium. These results indicate that LPA produced in the uterine endometrium may play a critical role in uterine endometrial function and conceptus development through EDG7-mediated PTGS2 expression during implantation and establishment of pregnancy in pigs.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2008-0354</identifier><identifier>PMID: 18703629</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Chevy Chase, MD: Endocrine Society</publisher><subject>Animals ; Biological and medical sciences ; Blotting, Northern ; Cyclooxygenase 2 - genetics ; Endometrium ; Endometrium - drug effects ; Endometrium - metabolism ; Epithelium ; Estrogens ; Estrous Cycle - physiology ; Estrus cycle ; Female ; Fundamental and applied biological sciences. Psychology ; G protein-coupled receptors ; Gene expression ; Gene Expression - drug effects ; Hormones ; Implantation ; In Situ Hybridization ; Lysophosphatidic acid ; Lysophospholipids - metabolism ; Lysophospholipids - pharmacology ; mRNA ; Phospholipids ; Pregnancy ; Prostaglandin endoperoxide synthase ; Random Allocation ; Receptors ; Receptors, Estrogen - genetics ; Receptors, Lysophosphatidic Acid - genetics ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Steroid hormones ; Swine ; Uterus ; Uterus - drug effects ; Uterus - metabolism ; Vertebrates: endocrinology</subject><ispartof>Endocrinology (Philadelphia), 2008-12, Vol.149 (12), p.6166-6175</ispartof><rights>Copyright © 2008 by the Endocrine Society 2008</rights><rights>2009 INIST-CNRS</rights><rights>Copyright © 2008 by the Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c527t-cfd2d50e2816b196ecb5ec231c6f7f20efde1a6f1925100b0b7da916fc833ad3</citedby><cites>FETCH-LOGICAL-c527t-cfd2d50e2816b196ecb5ec231c6f7f20efde1a6f1925100b0b7da916fc833ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20939899$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18703629$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Seo, Heewon</creatorcontrib><creatorcontrib>Kim, Mingoo</creatorcontrib><creatorcontrib>Choi, Yohan</creatorcontrib><creatorcontrib>Lee, Chang-Kyu</creatorcontrib><creatorcontrib>Ka, Hakhyun</creatorcontrib><title>Analysis of Lysophosphatidic Acid (LPA) Receptor and LPA-Induced Endometrial Prostaglandin-Endoperoxide Synthase 2 Expression in the Porcine Uterus</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Lysophosphatidic acid (LPA), a simple phospholipid-derived mediator with diverse biological actions, acts through the specific G protein-coupled receptors endothelial differentiation gene (EDG) 2, EDG4, EDG7, and GPR23. Recent studies indicate a critical role for LPA receptor signaling in embryo implantation. To understand how LPA acts in the uterus during pregnancy in pigs, we evaluated: 1) spatial and temporal expression of LPA receptors in the uterine endometrium during the estrous cycle and pregnancy and in early-stage concepti, 2) LPA levels in uterine luminal fluids from d 12 of the estrous cycle and pregnancy, 3) effects of steroid hormones on EDG7 mRNA levels, and 4) effects of LPA on prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA levels in the uterine endometrium using explant cultures. Of the four receptors, EDG7 was dominant, and its expression was regulated by pregnancy stage and status. EDG7 expression was highest on d 12 pregnancy, and localized to the luminal and glandular epithelium, and EDG7 mRNA levels were elevated by estrogen in the endometrium. EDG7 expression was also detected in concepti of d 12 and 15. LPA with various fatty acyl groups was present in the uterine lumen on d 12 of both the estrous cycle and pregnancy. LPA increased PTGS2 mRNA abundance in the uterine endometrium. These results indicate that LPA produced in the uterine endometrium may play a critical role in uterine endometrial function and conceptus development through EDG7-mediated PTGS2 expression during implantation and establishment of pregnancy in pigs.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blotting, Northern</subject><subject>Cyclooxygenase 2 - genetics</subject><subject>Endometrium</subject><subject>Endometrium - drug effects</subject><subject>Endometrium - metabolism</subject><subject>Epithelium</subject><subject>Estrogens</subject><subject>Estrous Cycle - physiology</subject><subject>Estrus cycle</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>G protein-coupled receptors</subject><subject>Gene expression</subject><subject>Gene Expression - drug effects</subject><subject>Hormones</subject><subject>Implantation</subject><subject>In Situ Hybridization</subject><subject>Lysophosphatidic acid</subject><subject>Lysophospholipids - metabolism</subject><subject>Lysophospholipids - pharmacology</subject><subject>mRNA</subject><subject>Phospholipids</subject><subject>Pregnancy</subject><subject>Prostaglandin endoperoxide synthase</subject><subject>Random Allocation</subject><subject>Receptors</subject><subject>Receptors, Estrogen - genetics</subject><subject>Receptors, Lysophosphatidic Acid - genetics</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Steroid hormones</subject><subject>Swine</subject><subject>Uterus</subject><subject>Uterus - drug effects</subject><subject>Uterus - metabolism</subject><subject>Vertebrates: endocrinology</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kVtrFDEYhoNY7Lp657UERGvBqTnMKZdL2drCgovW6yGTfHFTZpNpMgPd3-EfNuMOFsRehSQP3-F9EHpDyQVllHwGd8EIqTPCi_wZWlCRF1lFK_IcLQihPKsYq07Ryxjv0jXPc_4CndK6IrxkYoF-rZzsDtFG7A3eHKLvdz72OzlYbRVeKavxx812dY6_gYJ-8AFLp3F6yW6cHhVovHba72EIVnZ4G3wc5M8uMdZl008PwT9YDfj7wQ07GQEzvH7oA8RovcPW4WEHeOuDsg7wjwHCGF-hEyO7CK_nc4lur9a3l9fZ5uuXm8vVJlMFq4ZMGc10QYDVtGypKEG1BSjGqSpNZRgBo4HK0lDBCkpIS9pKS0FLo2rOpeZL9OFYtg_-foQ4NHsbFXRpevBjbEpRMyJYlcB3_4B3fgwpt9hwykkhiEhxLtGnI6VSCDGAafpg9zIcGkqayVQDrplMNZOphL-di47tHvQjPKtJwPsZkFHJzgTplI1_uTQaF7WYuLMj58f-qZbZ3JIfSUhiVEiB__HwuM1_B_0NbHS5uw</recordid><startdate>20081201</startdate><enddate>20081201</enddate><creator>Seo, Heewon</creator><creator>Kim, Mingoo</creator><creator>Choi, Yohan</creator><creator>Lee, Chang-Kyu</creator><creator>Ka, Hakhyun</creator><general>Endocrine Society</general><general>Oxford University Press</general><scope>IQODW</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>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20081201</creationdate><title>Analysis of Lysophosphatidic Acid (LPA) Receptor and LPA-Induced Endometrial Prostaglandin-Endoperoxide Synthase 2 Expression in the Porcine Uterus</title><author>Seo, Heewon ; Kim, Mingoo ; Choi, Yohan ; Lee, Chang-Kyu ; Ka, Hakhyun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c527t-cfd2d50e2816b196ecb5ec231c6f7f20efde1a6f1925100b0b7da916fc833ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blotting, Northern</topic><topic>Cyclooxygenase 2 - genetics</topic><topic>Endometrium</topic><topic>Endometrium - drug effects</topic><topic>Endometrium - metabolism</topic><topic>Epithelium</topic><topic>Estrogens</topic><topic>Estrous Cycle - physiology</topic><topic>Estrus cycle</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>G protein-coupled receptors</topic><topic>Gene expression</topic><topic>Gene Expression - drug effects</topic><topic>Hormones</topic><topic>Implantation</topic><topic>In Situ Hybridization</topic><topic>Lysophosphatidic acid</topic><topic>Lysophospholipids - metabolism</topic><topic>Lysophospholipids - pharmacology</topic><topic>mRNA</topic><topic>Phospholipids</topic><topic>Pregnancy</topic><topic>Prostaglandin endoperoxide synthase</topic><topic>Random Allocation</topic><topic>Receptors</topic><topic>Receptors, Estrogen - genetics</topic><topic>Receptors, Lysophosphatidic Acid - genetics</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Steroid hormones</topic><topic>Swine</topic><topic>Uterus</topic><topic>Uterus - drug effects</topic><topic>Uterus - metabolism</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Seo, Heewon</creatorcontrib><creatorcontrib>Kim, Mingoo</creatorcontrib><creatorcontrib>Choi, Yohan</creatorcontrib><creatorcontrib>Lee, Chang-Kyu</creatorcontrib><creatorcontrib>Ka, Hakhyun</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Seo, Heewon</au><au>Kim, Mingoo</au><au>Choi, Yohan</au><au>Lee, Chang-Kyu</au><au>Ka, Hakhyun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of Lysophosphatidic Acid (LPA) Receptor and LPA-Induced Endometrial Prostaglandin-Endoperoxide Synthase 2 Expression in the Porcine Uterus</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2008-12-01</date><risdate>2008</risdate><volume>149</volume><issue>12</issue><spage>6166</spage><epage>6175</epage><pages>6166-6175</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>Lysophosphatidic acid (LPA), a simple phospholipid-derived mediator with diverse biological actions, acts through the specific G protein-coupled receptors endothelial differentiation gene (EDG) 2, EDG4, EDG7, and GPR23. Recent studies indicate a critical role for LPA receptor signaling in embryo implantation. To understand how LPA acts in the uterus during pregnancy in pigs, we evaluated: 1) spatial and temporal expression of LPA receptors in the uterine endometrium during the estrous cycle and pregnancy and in early-stage concepti, 2) LPA levels in uterine luminal fluids from d 12 of the estrous cycle and pregnancy, 3) effects of steroid hormones on EDG7 mRNA levels, and 4) effects of LPA on prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA levels in the uterine endometrium using explant cultures. Of the four receptors, EDG7 was dominant, and its expression was regulated by pregnancy stage and status. EDG7 expression was highest on d 12 pregnancy, and localized to the luminal and glandular epithelium, and EDG7 mRNA levels were elevated by estrogen in the endometrium. EDG7 expression was also detected in concepti of d 12 and 15. LPA with various fatty acyl groups was present in the uterine lumen on d 12 of both the estrous cycle and pregnancy. LPA increased PTGS2 mRNA abundance in the uterine endometrium. These results indicate that LPA produced in the uterine endometrium may play a critical role in uterine endometrial function and conceptus development through EDG7-mediated PTGS2 expression during implantation and establishment of pregnancy in pigs.</abstract><cop>Chevy Chase, MD</cop><pub>Endocrine Society</pub><pmid>18703629</pmid><doi>10.1210/en.2008-0354</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0013-7227 |
| ispartof | Endocrinology (Philadelphia), 2008-12, Vol.149 (12), p.6166-6175 |
| issn | 0013-7227 1945-7170 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_69820927 |
| source | MEDLINE; Oxford Journals - Connect here FIRST to enable access; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Animals Biological and medical sciences Blotting, Northern Cyclooxygenase 2 - genetics Endometrium Endometrium - drug effects Endometrium - metabolism Epithelium Estrogens Estrous Cycle - physiology Estrus cycle Female Fundamental and applied biological sciences. Psychology G protein-coupled receptors Gene expression Gene Expression - drug effects Hormones Implantation In Situ Hybridization Lysophosphatidic acid Lysophospholipids - metabolism Lysophospholipids - pharmacology mRNA Phospholipids Pregnancy Prostaglandin endoperoxide synthase Random Allocation Receptors Receptors, Estrogen - genetics Receptors, Lysophosphatidic Acid - genetics Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics RNA, Messenger - metabolism Steroid hormones Swine Uterus Uterus - drug effects Uterus - metabolism Vertebrates: endocrinology |
| title | Analysis of Lysophosphatidic Acid (LPA) Receptor and LPA-Induced Endometrial Prostaglandin-Endoperoxide Synthase 2 Expression in the Porcine Uterus |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T18%3A15%3A56IST&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=Analysis%20of%20Lysophosphatidic%20Acid%20(LPA)%20Receptor%20and%20LPA-Induced%20Endometrial%20Prostaglandin-Endoperoxide%20Synthase%202%20Expression%20in%20the%20Porcine%20Uterus&rft.jtitle=Endocrinology%20(Philadelphia)&rft.au=Seo,%20Heewon&rft.date=2008-12-01&rft.volume=149&rft.issue=12&rft.spage=6166&rft.epage=6175&rft.pages=6166-6175&rft.issn=0013-7227&rft.eissn=1945-7170&rft.coden=ENDOAO&rft_id=info:doi/10.1210/en.2008-0354&rft_dat=%3Cproquest_cross%3E69820927%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=3130590970&rft_id=info:pmid/18703629&rft_oup_id=10.1210/en.2008-0354&rfr_iscdi=true |