Increased Phosphorylation of Myosin Light Chain Prevents in Vitro Decidualization
Differentiation of stromal cells into decidual cells, which is critical to successful pregnancy, represents a complex transformation requiring changes in cytoskeletal architecture. We demonstrate that in vitro differentiation of human uterine fibroblasts into decidual cells includes down-regulation...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 2007-07, Vol.148 (7), p.3176-3184 |
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| creator | Ihnatovych, Ivanna Hu, WenYang Martin, Jody L Fazleabas, Asgerally T de Lanerolle, Primal Strakova, Zuzana |
| description | Differentiation of stromal cells into decidual cells, which is critical to successful pregnancy, represents a complex transformation requiring changes in cytoskeletal architecture. We demonstrate that in vitro differentiation of human uterine fibroblasts into decidual cells includes down-regulation of α-smooth muscle actin and β-tubulin, phosphorylation of focal adhesion kinase, and redistribution of vinculin. This is accompanied by varied adhesion to fibronectin and a modified ability to migrate. Cytoskeletal organization is determined primarily by actin-myosin II interactions governed by the phosphorylation of myosin light chain (MLC20). Decidualization induced by cAMP [with estradiol-17β (E) and medroxyprogesterone acetate (P)] results in a 40% decrease in MLC20 phosphorylation and a 55% decline in the long (214 kDa) form of myosin light-chain kinase (MLCK). Destabilization of the cytoskeleton by inhibitors of MLCK (ML-7) or myosin II ATPase (blebbistatin) accelerates decidualization induced by cAMP (with E and P) but inhibits decidualization induced by IL-1β (with E and P). Adenoviral infection of human uterine fibroblast cells with a constitutively active form of MLCK followed by decidualization stimuli leads to a 30% increase in MLC20 phosphorylation and prevents decidualization. These data provide evidence that the regulation of cytoskeletal dynamics by MLC20 phosphorylation is critical for decidualization. |
| doi_str_mv | 10.1210/en.2006-1673 |
| format | Article |
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We demonstrate that in vitro differentiation of human uterine fibroblasts into decidual cells includes down-regulation of α-smooth muscle actin and β-tubulin, phosphorylation of focal adhesion kinase, and redistribution of vinculin. This is accompanied by varied adhesion to fibronectin and a modified ability to migrate. Cytoskeletal organization is determined primarily by actin-myosin II interactions governed by the phosphorylation of myosin light chain (MLC20). Decidualization induced by cAMP [with estradiol-17β (E) and medroxyprogesterone acetate (P)] results in a 40% decrease in MLC20 phosphorylation and a 55% decline in the long (214 kDa) form of myosin light-chain kinase (MLCK). Destabilization of the cytoskeleton by inhibitors of MLCK (ML-7) or myosin II ATPase (blebbistatin) accelerates decidualization induced by cAMP (with E and P) but inhibits decidualization induced by IL-1β (with E and P). Adenoviral infection of human uterine fibroblast cells with a constitutively active form of MLCK followed by decidualization stimuli leads to a 30% increase in MLC20 phosphorylation and prevents decidualization. These data provide evidence that the regulation of cytoskeletal dynamics by MLC20 phosphorylation is critical for decidualization.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2006-1673</identifier><identifier>PMID: 17412815</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>17β-Estradiol ; Acetic acid ; Actin ; Actins - metabolism ; Adhesion ; Biological and medical sciences ; Cell Adhesion - drug effects ; Cell differentiation ; Cell Differentiation - drug effects ; Cell Movement - drug effects ; Cells, Cultured ; Cyclic AMP ; Cyclic AMP - pharmacology ; Cytoskeleton ; Cytoskeleton - metabolism ; Decidua ; Destabilization ; Differentiation ; Endometrium - cytology ; Endometrium - drug effects ; Endometrium - metabolism ; Female ; Fibroblasts ; Fibroblasts - cytology ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; Fibronectin ; Focal adhesion kinase ; Fundamental and applied biological sciences. Psychology ; Humans ; Interleukin-1beta - pharmacology ; Kinases ; Medroxyprogesterone acetate ; Models, Biological ; Myosin ; Myosin Light Chains - metabolism ; Myosin-light-chain kinase ; Phosphorylation ; Phosphorylation - drug effects ; Pregnancy ; Sex hormones ; Smooth muscle ; Stromal cells ; Tubulin ; Tubulin - metabolism ; Uterus ; Uterus - cytology ; Uterus - drug effects ; Uterus - metabolism ; Vertebrates: endocrinology ; Vinculin</subject><ispartof>Endocrinology (Philadelphia), 2007-07, Vol.148 (7), p.3176-3184</ispartof><rights>Copyright © 2007 by The Endocrine Society 2007</rights><rights>2007 INIST-CNRS</rights><rights>Copyright © 2007 by The Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c527t-8e222f8e7103cdef7f1fab6fe08ac386cd8fc406ce4ab1165531c45ee2aaab0d3</citedby><cites>FETCH-LOGICAL-c527t-8e222f8e7103cdef7f1fab6fe08ac386cd8fc406ce4ab1165531c45ee2aaab0d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18859451$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17412815$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ihnatovych, Ivanna</creatorcontrib><creatorcontrib>Hu, WenYang</creatorcontrib><creatorcontrib>Martin, Jody L</creatorcontrib><creatorcontrib>Fazleabas, Asgerally T</creatorcontrib><creatorcontrib>de Lanerolle, Primal</creatorcontrib><creatorcontrib>Strakova, Zuzana</creatorcontrib><title>Increased Phosphorylation of Myosin Light Chain Prevents in Vitro Decidualization</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Differentiation of stromal cells into decidual cells, which is critical to successful pregnancy, represents a complex transformation requiring changes in cytoskeletal architecture. We demonstrate that in vitro differentiation of human uterine fibroblasts into decidual cells includes down-regulation of α-smooth muscle actin and β-tubulin, phosphorylation of focal adhesion kinase, and redistribution of vinculin. This is accompanied by varied adhesion to fibronectin and a modified ability to migrate. Cytoskeletal organization is determined primarily by actin-myosin II interactions governed by the phosphorylation of myosin light chain (MLC20). Decidualization induced by cAMP [with estradiol-17β (E) and medroxyprogesterone acetate (P)] results in a 40% decrease in MLC20 phosphorylation and a 55% decline in the long (214 kDa) form of myosin light-chain kinase (MLCK). Destabilization of the cytoskeleton by inhibitors of MLCK (ML-7) or myosin II ATPase (blebbistatin) accelerates decidualization induced by cAMP (with E and P) but inhibits decidualization induced by IL-1β (with E and P). Adenoviral infection of human uterine fibroblast cells with a constitutively active form of MLCK followed by decidualization stimuli leads to a 30% increase in MLC20 phosphorylation and prevents decidualization. These data provide evidence that the regulation of cytoskeletal dynamics by MLC20 phosphorylation is critical for decidualization.</description><subject>17β-Estradiol</subject><subject>Acetic acid</subject><subject>Actin</subject><subject>Actins - metabolism</subject><subject>Adhesion</subject><subject>Biological and medical sciences</subject><subject>Cell Adhesion - drug effects</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Movement - drug effects</subject><subject>Cells, Cultured</subject><subject>Cyclic AMP</subject><subject>Cyclic AMP - pharmacology</subject><subject>Cytoskeleton</subject><subject>Cytoskeleton - metabolism</subject><subject>Decidua</subject><subject>Destabilization</subject><subject>Differentiation</subject><subject>Endometrium - cytology</subject><subject>Endometrium - drug effects</subject><subject>Endometrium - metabolism</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - metabolism</subject><subject>Fibronectin</subject><subject>Focal adhesion kinase</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Interleukin-1beta - pharmacology</subject><subject>Kinases</subject><subject>Medroxyprogesterone acetate</subject><subject>Models, Biological</subject><subject>Myosin</subject><subject>Myosin Light Chains - metabolism</subject><subject>Myosin-light-chain kinase</subject><subject>Phosphorylation</subject><subject>Phosphorylation - drug effects</subject><subject>Pregnancy</subject><subject>Sex hormones</subject><subject>Smooth muscle</subject><subject>Stromal cells</subject><subject>Tubulin</subject><subject>Tubulin - metabolism</subject><subject>Uterus</subject><subject>Uterus - cytology</subject><subject>Uterus - drug effects</subject><subject>Uterus - metabolism</subject><subject>Vertebrates: endocrinology</subject><subject>Vinculin</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10c9rFDEUB_Agit1Wb55lQKwXp-Ylk0k8yvqjhRUrqNeQzby4KbPJNJkprH99s-7AgthTEvjkvZdvCHkB9AIY0HcYLhilbQ2t5I_IAt43opYg6WOyoBR4LRmTJ-Q055tybJqGPyUnIBtgCsSCfL8KNqHJ2FXXm5iHTUy73ow-hiq66usuZh-qlf-9GavlxpT9dcI7DGOuyv6XH1OsPqL13WR6_-fvvWfkiTN9xufzekZ-fv70Y3lZr759uVp-WNVWMDnWChljTqEEym2HTjpwZt06pMpYrlrbKWcb2lpszBqgFYKDbQQiM8asacfPyPmh7pDi7YR51FufLfa9CRinrCVtqWg4L_DVP_AmTimU2TQHToVSwGhRbw_KpphzQqeH5Lcm7TRQvQ9aY9D7oPU-6MJfzkWn9Ra7I56TLeD1DEy2pnfJBOvz0Sklyk9BcW8OLk7DQy3ruSU_SAxdtMkHHBLmfHzNfwe9B1DEoxE</recordid><startdate>20070701</startdate><enddate>20070701</enddate><creator>Ihnatovych, Ivanna</creator><creator>Hu, WenYang</creator><creator>Martin, Jody L</creator><creator>Fazleabas, Asgerally T</creator><creator>de Lanerolle, Primal</creator><creator>Strakova, Zuzana</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>20070701</creationdate><title>Increased Phosphorylation of Myosin Light Chain Prevents in Vitro Decidualization</title><author>Ihnatovych, Ivanna ; Hu, WenYang ; Martin, Jody L ; Fazleabas, Asgerally T ; de Lanerolle, Primal ; Strakova, Zuzana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c527t-8e222f8e7103cdef7f1fab6fe08ac386cd8fc406ce4ab1165531c45ee2aaab0d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>17β-Estradiol</topic><topic>Acetic acid</topic><topic>Actin</topic><topic>Actins - metabolism</topic><topic>Adhesion</topic><topic>Biological and medical sciences</topic><topic>Cell Adhesion - drug effects</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Movement - drug effects</topic><topic>Cells, Cultured</topic><topic>Cyclic AMP</topic><topic>Cyclic AMP - pharmacology</topic><topic>Cytoskeleton</topic><topic>Cytoskeleton - metabolism</topic><topic>Decidua</topic><topic>Destabilization</topic><topic>Differentiation</topic><topic>Endometrium - cytology</topic><topic>Endometrium - drug effects</topic><topic>Endometrium - metabolism</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - metabolism</topic><topic>Fibronectin</topic><topic>Focal adhesion kinase</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Interleukin-1beta - pharmacology</topic><topic>Kinases</topic><topic>Medroxyprogesterone acetate</topic><topic>Models, Biological</topic><topic>Myosin</topic><topic>Myosin Light Chains - metabolism</topic><topic>Myosin-light-chain kinase</topic><topic>Phosphorylation</topic><topic>Phosphorylation - drug effects</topic><topic>Pregnancy</topic><topic>Sex hormones</topic><topic>Smooth muscle</topic><topic>Stromal cells</topic><topic>Tubulin</topic><topic>Tubulin - metabolism</topic><topic>Uterus</topic><topic>Uterus - cytology</topic><topic>Uterus - drug effects</topic><topic>Uterus - metabolism</topic><topic>Vertebrates: endocrinology</topic><topic>Vinculin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ihnatovych, Ivanna</creatorcontrib><creatorcontrib>Hu, WenYang</creatorcontrib><creatorcontrib>Martin, Jody L</creatorcontrib><creatorcontrib>Fazleabas, Asgerally T</creatorcontrib><creatorcontrib>de Lanerolle, Primal</creatorcontrib><creatorcontrib>Strakova, Zuzana</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>Ihnatovych, Ivanna</au><au>Hu, WenYang</au><au>Martin, Jody L</au><au>Fazleabas, Asgerally T</au><au>de Lanerolle, Primal</au><au>Strakova, Zuzana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased Phosphorylation of Myosin Light Chain Prevents in Vitro Decidualization</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2007-07-01</date><risdate>2007</risdate><volume>148</volume><issue>7</issue><spage>3176</spage><epage>3184</epage><pages>3176-3184</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>Differentiation of stromal cells into decidual cells, which is critical to successful pregnancy, represents a complex transformation requiring changes in cytoskeletal architecture. We demonstrate that in vitro differentiation of human uterine fibroblasts into decidual cells includes down-regulation of α-smooth muscle actin and β-tubulin, phosphorylation of focal adhesion kinase, and redistribution of vinculin. This is accompanied by varied adhesion to fibronectin and a modified ability to migrate. Cytoskeletal organization is determined primarily by actin-myosin II interactions governed by the phosphorylation of myosin light chain (MLC20). Decidualization induced by cAMP [with estradiol-17β (E) and medroxyprogesterone acetate (P)] results in a 40% decrease in MLC20 phosphorylation and a 55% decline in the long (214 kDa) form of myosin light-chain kinase (MLCK). Destabilization of the cytoskeleton by inhibitors of MLCK (ML-7) or myosin II ATPase (blebbistatin) accelerates decidualization induced by cAMP (with E and P) but inhibits decidualization induced by IL-1β (with E and P). Adenoviral infection of human uterine fibroblast cells with a constitutively active form of MLCK followed by decidualization stimuli leads to a 30% increase in MLC20 phosphorylation and prevents decidualization. These data provide evidence that the regulation of cytoskeletal dynamics by MLC20 phosphorylation is critical for decidualization.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>17412815</pmid><doi>10.1210/en.2006-1673</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 17β-Estradiol Acetic acid Actin Actins - metabolism Adhesion Biological and medical sciences Cell Adhesion - drug effects Cell differentiation Cell Differentiation - drug effects Cell Movement - drug effects Cells, Cultured Cyclic AMP Cyclic AMP - pharmacology Cytoskeleton Cytoskeleton - metabolism Decidua Destabilization Differentiation Endometrium - cytology Endometrium - drug effects Endometrium - metabolism Female Fibroblasts Fibroblasts - cytology Fibroblasts - drug effects Fibroblasts - metabolism Fibronectin Focal adhesion kinase Fundamental and applied biological sciences. Psychology Humans Interleukin-1beta - pharmacology Kinases Medroxyprogesterone acetate Models, Biological Myosin Myosin Light Chains - metabolism Myosin-light-chain kinase Phosphorylation Phosphorylation - drug effects Pregnancy Sex hormones Smooth muscle Stromal cells Tubulin Tubulin - metabolism Uterus Uterus - cytology Uterus - drug effects Uterus - metabolism Vertebrates: endocrinology Vinculin |
| title | Increased Phosphorylation of Myosin Light Chain Prevents in Vitro Decidualization |
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