Antiproliferative Action of Progesterone in Uterine Epithelium Is Mediated by Hand2
During pregnancy, progesterone inhibits the growth-promoting actions of estrogen in the uterus. However, the mechanism for this is not clear. The attenuation of estrogen-mediated proliferation of the uterine epithelium by progesterone is a prerequisite for successful implantation. Our study reveals...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2011-02, Vol.331 (6019), p.912-916 |
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| creator | Li, Quanxi Kannan, Athilakshmi DeMayo, Francesco J Lydon, John P Cooke, Paul S Yamagishi, Hiroyuki Srivastava, Deepak Bagchi, Milan K Bagchi, Indrani C |
| description | During pregnancy, progesterone inhibits the growth-promoting actions of estrogen in the uterus. However, the mechanism for this is not clear. The attenuation of estrogen-mediated proliferation of the uterine epithelium by progesterone is a prerequisite for successful implantation. Our study reveals that progesterone-induced expression of the basic helix-loop-helix transcription factor Hand2 in the uterine stroma suppresses the production of several fibroblast growth factors (FGFs) that act as paracrine mediators of mitogenic effects of estrogen on the epithelium. In mouse uteri lacking Hand2, continued induction of these FGFs in the stroma maintains epithelial proliferation and stimulates estrogen-induced pathways, resulting in impaired implantation. Thus, Hand2 is a critical regulator of the uterine stromal-epithelial communication that directs proper steroid regulation conducive for the establishment of pregnancy. |
| doi_str_mv | 10.1126/science.1197454 |
| format | Article |
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However, the mechanism for this is not clear. The attenuation of estrogen-mediated proliferation of the uterine epithelium by progesterone is a prerequisite for successful implantation. Our study reveals that progesterone-induced expression of the basic helix-loop-helix transcription factor Hand2 in the uterine stroma suppresses the production of several fibroblast growth factors (FGFs) that act as paracrine mediators of mitogenic effects of estrogen on the epithelium. In mouse uteri lacking Hand2, continued induction of these FGFs in the stroma maintains epithelial proliferation and stimulates estrogen-induced pathways, resulting in impaired implantation. Thus, Hand2 is a critical regulator of the uterine stromal-epithelial communication that directs proper steroid regulation conducive for the establishment of pregnancy.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1197454</identifier><identifier>PMID: 21330545</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Animals ; Attenuation ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Biological and medical sciences ; Cell Proliferation ; Control ; Embryo Implantation - physiology ; Embryos ; Endometrium - drug effects ; Endometrium - metabolism ; Epithelial cells ; Epithelial Cells - cytology ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Epithelium ; Epithelium - metabolism ; Estradiol - metabolism ; Estrogen Receptor alpha - metabolism ; Estrogens ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Female ; Fibroblast Growth Factors - genetics ; Fibroblast Growth Factors - metabolism ; Fibroblasts ; Fundamental and applied biological sciences. Psychology ; Gene Expression Profiling ; Hormone metabolism and regulation ; Implantation ; Mammalian female genital system ; Messenger RNA ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mifepristone - pharmacology ; Mucin-1 - metabolism ; Phosphorylation ; Pregnancy ; Progesterone - antagonists & inhibitors ; Progesterone - metabolism ; Progesterone - pharmacology ; Receptors, Fibroblast Growth Factor - metabolism ; Receptors, Progesterone - metabolism ; Signal Transduction ; Steroids ; Stromal cells ; Stromal Cells - cytology ; Stromal Cells - metabolism ; Transcription, Genetic ; Uterus ; Vehicles ; Vertebrates: reproduction</subject><ispartof>Science (American Association for the Advancement of Science), 2011-02, Vol.331 (6019), p.912-916</ispartof><rights>Copyright © 2011 American Association for the Advancement of Science</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c593t-f8d9669b39e976ac1fd548401e50f0743988278327b12764921bc4c515b0c03d3</citedby><cites>FETCH-LOGICAL-c593t-f8d9669b39e976ac1fd548401e50f0743988278327b12764921bc4c515b0c03d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25790352$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25790352$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,776,780,799,881,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23911307$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21330545$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Quanxi</creatorcontrib><creatorcontrib>Kannan, Athilakshmi</creatorcontrib><creatorcontrib>DeMayo, Francesco J</creatorcontrib><creatorcontrib>Lydon, John P</creatorcontrib><creatorcontrib>Cooke, Paul S</creatorcontrib><creatorcontrib>Yamagishi, Hiroyuki</creatorcontrib><creatorcontrib>Srivastava, Deepak</creatorcontrib><creatorcontrib>Bagchi, Milan K</creatorcontrib><creatorcontrib>Bagchi, Indrani C</creatorcontrib><title>Antiproliferative Action of Progesterone in Uterine Epithelium Is Mediated by Hand2</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>During pregnancy, progesterone inhibits the growth-promoting actions of estrogen in the uterus. However, the mechanism for this is not clear. The attenuation of estrogen-mediated proliferation of the uterine epithelium by progesterone is a prerequisite for successful implantation. Our study reveals that progesterone-induced expression of the basic helix-loop-helix transcription factor Hand2 in the uterine stroma suppresses the production of several fibroblast growth factors (FGFs) that act as paracrine mediators of mitogenic effects of estrogen on the epithelium. In mouse uteri lacking Hand2, continued induction of these FGFs in the stroma maintains epithelial proliferation and stimulates estrogen-induced pathways, resulting in impaired implantation. Thus, Hand2 is a critical regulator of the uterine stromal-epithelial communication that directs proper steroid regulation conducive for the establishment of pregnancy.</description><subject>Animals</subject><subject>Attenuation</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cell Proliferation</subject><subject>Control</subject><subject>Embryo Implantation - physiology</subject><subject>Embryos</subject><subject>Endometrium - drug effects</subject><subject>Endometrium - metabolism</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - cytology</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelium</subject><subject>Epithelium - metabolism</subject><subject>Estradiol - metabolism</subject><subject>Estrogen Receptor alpha - metabolism</subject><subject>Estrogens</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Female</subject><subject>Fibroblast Growth Factors - genetics</subject><subject>Fibroblast Growth Factors - metabolism</subject><subject>Fibroblasts</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Profiling</subject><subject>Hormone metabolism and regulation</subject><subject>Implantation</subject><subject>Mammalian female genital system</subject><subject>Messenger RNA</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mifepristone - pharmacology</subject><subject>Mucin-1 - metabolism</subject><subject>Phosphorylation</subject><subject>Pregnancy</subject><subject>Progesterone - antagonists & inhibitors</subject><subject>Progesterone - metabolism</subject><subject>Progesterone - pharmacology</subject><subject>Receptors, Fibroblast Growth Factor - metabolism</subject><subject>Receptors, Progesterone - metabolism</subject><subject>Signal Transduction</subject><subject>Steroids</subject><subject>Stromal cells</subject><subject>Stromal Cells - cytology</subject><subject>Stromal Cells - metabolism</subject><subject>Transcription, Genetic</subject><subject>Uterus</subject><subject>Vehicles</subject><subject>Vertebrates: reproduction</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9rFDEUx4Modl09e1IHoXga-5JMfl2EpbS2UFGoew6ZTGabZTbZJjOF_vem7NiqF0954ft5X957X4TeYviMMeEn2XoXrCsfJRrWPEMLDIrVigB9jhYAlNcSBDtCr3LeAhRN0ZfoiGBKgTVsga5XYfT7FAffu2RGf-eqlR19DFXsqx8pblweXYrBVT5U61L6Up7t_XjjBj_tqstcfXOdN6Prqva-ujChI6_Ri94M2b2Z3yVan5_9PL2or75_vTxdXdW2TDHWvewU56qlyinBjcV9xxrZAHYMehANVVISISkRLSaCN4rg1jaWYdaCBdrRJfpy8N1P7c511oUxmUHvk9-ZdK-j8fpvJfgbvYl3mlICkrFi8Gk2SPF2Kpvqnc_WDYMJLk5ZKxCKUsr4f0nJiCoZ4AfPj_-Q2zilUO6gJZdCCF48l-jkANkUc06ufxwag34IVs_B6jnY0vH-z10f-d9JFuB4Bky2ZuiTCdbnJ46W-SiIwr07cNs8xvSkM6GAMlL0Dwe9N1GbTSoe62sCpRerhjPJ6S-xx751</recordid><startdate>20110218</startdate><enddate>20110218</enddate><creator>Li, Quanxi</creator><creator>Kannan, Athilakshmi</creator><creator>DeMayo, Francesco J</creator><creator>Lydon, John P</creator><creator>Cooke, Paul S</creator><creator>Yamagishi, Hiroyuki</creator><creator>Srivastava, Deepak</creator><creator>Bagchi, Milan K</creator><creator>Bagchi, Indrani C</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><scope>FBQ</scope><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>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110218</creationdate><title>Antiproliferative Action of Progesterone in Uterine Epithelium Is Mediated by Hand2</title><author>Li, Quanxi ; Kannan, Athilakshmi ; DeMayo, Francesco J ; Lydon, John P ; Cooke, Paul S ; Yamagishi, Hiroyuki ; Srivastava, Deepak ; Bagchi, Milan K ; Bagchi, Indrani C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c593t-f8d9669b39e976ac1fd548401e50f0743988278327b12764921bc4c515b0c03d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Attenuation</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Basic Helix-Loop-Helix Transcription Factors - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cell Proliferation</topic><topic>Control</topic><topic>Embryo Implantation - physiology</topic><topic>Embryos</topic><topic>Endometrium - drug effects</topic><topic>Endometrium - metabolism</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - cytology</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelium</topic><topic>Epithelium - metabolism</topic><topic>Estradiol - metabolism</topic><topic>Estrogen Receptor alpha - metabolism</topic><topic>Estrogens</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Female</topic><topic>Fibroblast Growth Factors - genetics</topic><topic>Fibroblast Growth Factors - metabolism</topic><topic>Fibroblasts</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Profiling</topic><topic>Hormone metabolism and regulation</topic><topic>Implantation</topic><topic>Mammalian female genital system</topic><topic>Messenger RNA</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mifepristone - pharmacology</topic><topic>Mucin-1 - metabolism</topic><topic>Phosphorylation</topic><topic>Pregnancy</topic><topic>Progesterone - antagonists & inhibitors</topic><topic>Progesterone - metabolism</topic><topic>Progesterone - pharmacology</topic><topic>Receptors, Fibroblast Growth Factor - metabolism</topic><topic>Receptors, Progesterone - metabolism</topic><topic>Signal Transduction</topic><topic>Steroids</topic><topic>Stromal cells</topic><topic>Stromal Cells - cytology</topic><topic>Stromal Cells - metabolism</topic><topic>Transcription, Genetic</topic><topic>Uterus</topic><topic>Vehicles</topic><topic>Vertebrates: reproduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Quanxi</creatorcontrib><creatorcontrib>Kannan, Athilakshmi</creatorcontrib><creatorcontrib>DeMayo, Francesco J</creatorcontrib><creatorcontrib>Lydon, John P</creatorcontrib><creatorcontrib>Cooke, Paul S</creatorcontrib><creatorcontrib>Yamagishi, Hiroyuki</creatorcontrib><creatorcontrib>Srivastava, Deepak</creatorcontrib><creatorcontrib>Bagchi, Milan K</creatorcontrib><creatorcontrib>Bagchi, Indrani C</creatorcontrib><collection>AGRIS</collection><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>Aluminium Industry Abstracts</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Ecology Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Quanxi</au><au>Kannan, Athilakshmi</au><au>DeMayo, Francesco J</au><au>Lydon, John P</au><au>Cooke, Paul S</au><au>Yamagishi, Hiroyuki</au><au>Srivastava, Deepak</au><au>Bagchi, Milan K</au><au>Bagchi, Indrani C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antiproliferative Action of Progesterone in Uterine Epithelium Is Mediated by Hand2</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2011-02-18</date><risdate>2011</risdate><volume>331</volume><issue>6019</issue><spage>912</spage><epage>916</epage><pages>912-916</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>During pregnancy, progesterone inhibits the growth-promoting actions of estrogen in the uterus. However, the mechanism for this is not clear. The attenuation of estrogen-mediated proliferation of the uterine epithelium by progesterone is a prerequisite for successful implantation. Our study reveals that progesterone-induced expression of the basic helix-loop-helix transcription factor Hand2 in the uterine stroma suppresses the production of several fibroblast growth factors (FGFs) that act as paracrine mediators of mitogenic effects of estrogen on the epithelium. In mouse uteri lacking Hand2, continued induction of these FGFs in the stroma maintains epithelial proliferation and stimulates estrogen-induced pathways, resulting in impaired implantation. Thus, Hand2 is a critical regulator of the uterine stromal-epithelial communication that directs proper steroid regulation conducive for the establishment of pregnancy.</abstract><cop>Washington, DC</cop><pub>American Association for the Advancement of Science</pub><pmid>21330545</pmid><doi>10.1126/science.1197454</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE |
| subjects | Animals Attenuation Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - metabolism Biological and medical sciences Cell Proliferation Control Embryo Implantation - physiology Embryos Endometrium - drug effects Endometrium - metabolism Epithelial cells Epithelial Cells - cytology Epithelial Cells - drug effects Epithelial Cells - metabolism Epithelium Epithelium - metabolism Estradiol - metabolism Estrogen Receptor alpha - metabolism Estrogens Extracellular Signal-Regulated MAP Kinases - metabolism Female Fibroblast Growth Factors - genetics Fibroblast Growth Factors - metabolism Fibroblasts Fundamental and applied biological sciences. Psychology Gene Expression Profiling Hormone metabolism and regulation Implantation Mammalian female genital system Messenger RNA Mice Mice, Inbred C57BL Mice, Knockout Mifepristone - pharmacology Mucin-1 - metabolism Phosphorylation Pregnancy Progesterone - antagonists & inhibitors Progesterone - metabolism Progesterone - pharmacology Receptors, Fibroblast Growth Factor - metabolism Receptors, Progesterone - metabolism Signal Transduction Steroids Stromal cells Stromal Cells - cytology Stromal Cells - metabolism Transcription, Genetic Uterus Vehicles Vertebrates: reproduction |
| title | Antiproliferative Action of Progesterone in Uterine Epithelium Is Mediated by Hand2 |
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