Cross-talk between cAMP and MAPK pathways in HSD11B2 induction by hCG in placental trophoblasts
Overexposure of the fetus to glucocorticoids in gestation is detrimental to fetal development. The passage of maternal glucocorticoids into the fetal circulation is governed by 11beta-Hydroxysteroid Dehydrogenase Type 2 (HSD11B2) in the placental syncytiotrophoblasts. Human chorionic gonadotropin (h...
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description | Overexposure of the fetus to glucocorticoids in gestation is detrimental to fetal development. The passage of maternal glucocorticoids into the fetal circulation is governed by 11beta-Hydroxysteroid Dehydrogenase Type 2 (HSD11B2) in the placental syncytiotrophoblasts. Human chorionic gonadotropin (hCG) plays an important role in maintaining placental HSD11B2 expression via activation of the cAMP pathway. In this study, we investigated the relationship between the activation of the cAMP pathway by hCG and subsequent phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) or p38 mitogen-activated protein kinase (MAPK) pathways in the regulation of placental HSD11B2 expression in human placental syncytiotrophoblasts. We found that treatment of the placental syncytiotrophoblasts with either hCG or dibutyl cAMP (dbcAMP) could promote the phosphorylation of p38 and ERK1/2. Inhibition of p38 MAPK with SB203580 not only reduced the basal HSD11B2 mRNA and protein levels but also attenuated HSD11B2 levels induced by either hCG or dbcAMP. By contrast, inhibition of ERK1/2 with PD98059 increased the basal mRNA and protein levels of HSD11B2 and had no effect on HSD11B2 mRNA and protein levels induced by either hCG or dbcAMP. These data suggest that p38 MAPK is involved in both basal and hCG/cAMP-induced expression of HSD11B2, and ERK1/2 may play a role opposite to p38 MAPK at least in the basal expression of HSD11B2 in human placental syncytiotrophoblasts and that there is complicated cross-talk between hCG/cAMP and MAPK cascades in the regulation of placental HSD11B2 expression. |
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The passage of maternal glucocorticoids into the fetal circulation is governed by 11beta-Hydroxysteroid Dehydrogenase Type 2 (HSD11B2) in the placental syncytiotrophoblasts. Human chorionic gonadotropin (hCG) plays an important role in maintaining placental HSD11B2 expression via activation of the cAMP pathway. In this study, we investigated the relationship between the activation of the cAMP pathway by hCG and subsequent phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) or p38 mitogen-activated protein kinase (MAPK) pathways in the regulation of placental HSD11B2 expression in human placental syncytiotrophoblasts. We found that treatment of the placental syncytiotrophoblasts with either hCG or dibutyl cAMP (dbcAMP) could promote the phosphorylation of p38 and ERK1/2. Inhibition of p38 MAPK with SB203580 not only reduced the basal HSD11B2 mRNA and protein levels but also attenuated HSD11B2 levels induced by either hCG or dbcAMP. By contrast, inhibition of ERK1/2 with PD98059 increased the basal mRNA and protein levels of HSD11B2 and had no effect on HSD11B2 mRNA and protein levels induced by either hCG or dbcAMP. These data suggest that p38 MAPK is involved in both basal and hCG/cAMP-induced expression of HSD11B2, and ERK1/2 may play a role opposite to p38 MAPK at least in the basal expression of HSD11B2 in human placental syncytiotrophoblasts and that there is complicated cross-talk between hCG/cAMP and MAPK cascades in the regulation of placental HSD11B2 expression.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0107938</identifier><identifier>PMID: 25229504</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>11-beta-Hydroxysteroid Dehydrogenase Type 2 - biosynthesis ; 11β-Hydroxysteroid dehydrogenase ; Activation ; Apoptosis ; Binding sites ; Biology and Life Sciences ; Cascades ; Chorionic gonadotropin ; Chorionic Gonadotropin - pharmacology ; Chorionic gonadotropins ; Consent ; Cyclic AMP ; Cyclic AMP - chemistry ; Cyclic AMP - metabolism ; Cyclic AMP - pharmacology ; Dehydrogenases ; Enzyme Induction - drug effects ; Extracellular signal-regulated kinase ; Female ; Fetuses ; Gestation ; Glucocorticoids ; Glycoproteins ; Gonadotropins ; Hospitals ; Humans ; Inhibition ; Kinases ; Life sciences ; MAP kinase ; MAP Kinase Signaling System - drug effects ; Medicine and Health Sciences ; Mitogen-Activated Protein Kinases - metabolism ; mRNA ; Pathways ; Phosphorylation ; Phosphorylation - drug effects ; Pituitary (anterior) ; Placenta ; Pregnancy ; Protein kinase ; Proteins ; RNA ; Rodents ; Signal transduction ; Sp1 Transcription Factor - metabolism ; Trophoblasts ; Trophoblasts - cytology ; Trophoblasts - drug effects ; Trophoblasts - metabolism</subject><ispartof>PloS one, 2014-09, Vol.9 (9), p.e107938</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Shu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Shu et al 2014 Shu et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-2523a3634a722eea3bed3fec3ee30237c5554f196bbded351ad231bfda82723b3</citedby><cites>FETCH-LOGICAL-c692t-2523a3634a722eea3bed3fec3ee30237c5554f196bbded351ad231bfda82723b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4168233/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4168233/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25229504$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tasken, Kjetil</contributor><creatorcontrib>Shu, Qun</creatorcontrib><creatorcontrib>Li, Wenjiao</creatorcontrib><creatorcontrib>Li, Jianneng</creatorcontrib><creatorcontrib>Wang, Wangsheng</creatorcontrib><creatorcontrib>Liu, Chao</creatorcontrib><creatorcontrib>Sun, Kang</creatorcontrib><title>Cross-talk between cAMP and MAPK pathways in HSD11B2 induction by hCG in placental trophoblasts</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Overexposure of the fetus to glucocorticoids in gestation is detrimental to fetal development. The passage of maternal glucocorticoids into the fetal circulation is governed by 11beta-Hydroxysteroid Dehydrogenase Type 2 (HSD11B2) in the placental syncytiotrophoblasts. Human chorionic gonadotropin (hCG) plays an important role in maintaining placental HSD11B2 expression via activation of the cAMP pathway. In this study, we investigated the relationship between the activation of the cAMP pathway by hCG and subsequent phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) or p38 mitogen-activated protein kinase (MAPK) pathways in the regulation of placental HSD11B2 expression in human placental syncytiotrophoblasts. We found that treatment of the placental syncytiotrophoblasts with either hCG or dibutyl cAMP (dbcAMP) could promote the phosphorylation of p38 and ERK1/2. Inhibition of p38 MAPK with SB203580 not only reduced the basal HSD11B2 mRNA and protein levels but also attenuated HSD11B2 levels induced by either hCG or dbcAMP. By contrast, inhibition of ERK1/2 with PD98059 increased the basal mRNA and protein levels of HSD11B2 and had no effect on HSD11B2 mRNA and protein levels induced by either hCG or dbcAMP. These data suggest that p38 MAPK is involved in both basal and hCG/cAMP-induced expression of HSD11B2, and ERK1/2 may play a role opposite to p38 MAPK at least in the basal expression of HSD11B2 in human placental syncytiotrophoblasts and that there is complicated cross-talk between hCG/cAMP and MAPK cascades in the regulation of placental HSD11B2 expression.</description><subject>11-beta-Hydroxysteroid Dehydrogenase Type 2 - biosynthesis</subject><subject>11β-Hydroxysteroid dehydrogenase</subject><subject>Activation</subject><subject>Apoptosis</subject><subject>Binding sites</subject><subject>Biology and Life Sciences</subject><subject>Cascades</subject><subject>Chorionic gonadotropin</subject><subject>Chorionic Gonadotropin - pharmacology</subject><subject>Chorionic gonadotropins</subject><subject>Consent</subject><subject>Cyclic AMP</subject><subject>Cyclic AMP - chemistry</subject><subject>Cyclic AMP - metabolism</subject><subject>Cyclic AMP - pharmacology</subject><subject>Dehydrogenases</subject><subject>Enzyme Induction - drug effects</subject><subject>Extracellular signal-regulated kinase</subject><subject>Female</subject><subject>Fetuses</subject><subject>Gestation</subject><subject>Glucocorticoids</subject><subject>Glycoproteins</subject><subject>Gonadotropins</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Inhibition</subject><subject>Kinases</subject><subject>Life sciences</subject><subject>MAP kinase</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Medicine and Health Sciences</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>mRNA</subject><subject>Pathways</subject><subject>Phosphorylation</subject><subject>Phosphorylation - drug effects</subject><subject>Pituitary (anterior)</subject><subject>Placenta</subject><subject>Pregnancy</subject><subject>Protein kinase</subject><subject>Proteins</subject><subject>RNA</subject><subject>Rodents</subject><subject>Signal transduction</subject><subject>Sp1 Transcription Factor - metabolism</subject><subject>Trophoblasts</subject><subject>Trophoblasts - cytology</subject><subject>Trophoblasts - drug effects</subject><subject>Trophoblasts - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNklFv0zAUhSMEYqPwDxBEQkLiocX2jZ3kZVIpsFVs2sSAV-vGcZqMNA6xw-i_x6HZ1EggIT_Y8v3u8fHVCYLnlCwoxPTtjem7ButFaxq9IJTEKSQPgmOaApsLRuDhwfkoeGLtDSEcEiEeB0eMM5ZyEh0HctUZa-cO6-9hpt2t1k2olhdXITZ5eLG8-hS26Mpb3NmwasKz6_eUvmP-mPfKVaYJs11Yrk6HWluj0o0XCl1n2tJkNVpnnwaPCqytfjbus-Drxw9fVmfz88vT9Wp5PlciZW7uDQGCgAhjxrRGyHQOhVagNRAGseKcRwVNRZblvsIp5gxoVuSYsJhBBrPg5V63rY2V42yspFwwwXnKYk-s90Ru8Ea2XbXFbicNVvLPhek2EjtXqVpLUiRc8Bh4ypOIgvJmElXQhOiMQu5dzYKT8bU-2-p8-HeH9UR0WmmqUm7MTxlRkTAAL_BqFOjMj15b9w_LI7VB76pqCuPF1LaySi4jmkQsikTiqcVfKL9yva2UT0dR-ftJw5tJg2ec_uU22Fsr19ef_5-9_DZlXx-wpcbaldbU_RAUOwWjPaiG8HW6uJ8cJXII99005BBuOYbbt704nPp9012a4TcwNvMb</recordid><startdate>20140917</startdate><enddate>20140917</enddate><creator>Shu, Qun</creator><creator>Li, Wenjiao</creator><creator>Li, Jianneng</creator><creator>Wang, Wangsheng</creator><creator>Liu, Chao</creator><creator>Sun, Kang</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140917</creationdate><title>Cross-talk between cAMP and MAPK pathways in HSD11B2 induction by hCG in placental trophoblasts</title><author>Shu, Qun ; Li, Wenjiao ; Li, Jianneng ; Wang, Wangsheng ; Liu, Chao ; Sun, Kang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-2523a3634a722eea3bed3fec3ee30237c5554f196bbded351ad231bfda82723b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>11-beta-Hydroxysteroid Dehydrogenase Type 2 - biosynthesis</topic><topic>11β-Hydroxysteroid dehydrogenase</topic><topic>Activation</topic><topic>Apoptosis</topic><topic>Binding sites</topic><topic>Biology and Life Sciences</topic><topic>Cascades</topic><topic>Chorionic gonadotropin</topic><topic>Chorionic Gonadotropin - pharmacology</topic><topic>Chorionic gonadotropins</topic><topic>Consent</topic><topic>Cyclic AMP</topic><topic>Cyclic AMP - chemistry</topic><topic>Cyclic AMP - metabolism</topic><topic>Cyclic AMP - pharmacology</topic><topic>Dehydrogenases</topic><topic>Enzyme Induction - drug effects</topic><topic>Extracellular signal-regulated kinase</topic><topic>Female</topic><topic>Fetuses</topic><topic>Gestation</topic><topic>Glucocorticoids</topic><topic>Glycoproteins</topic><topic>Gonadotropins</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Inhibition</topic><topic>Kinases</topic><topic>Life sciences</topic><topic>MAP kinase</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Medicine and Health Sciences</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>mRNA</topic><topic>Pathways</topic><topic>Phosphorylation</topic><topic>Phosphorylation - drug effects</topic><topic>Pituitary (anterior)</topic><topic>Placenta</topic><topic>Pregnancy</topic><topic>Protein kinase</topic><topic>Proteins</topic><topic>RNA</topic><topic>Rodents</topic><topic>Signal transduction</topic><topic>Sp1 Transcription Factor - metabolism</topic><topic>Trophoblasts</topic><topic>Trophoblasts - cytology</topic><topic>Trophoblasts - drug effects</topic><topic>Trophoblasts - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shu, Qun</creatorcontrib><creatorcontrib>Li, Wenjiao</creatorcontrib><creatorcontrib>Li, Jianneng</creatorcontrib><creatorcontrib>Wang, Wangsheng</creatorcontrib><creatorcontrib>Liu, Chao</creatorcontrib><creatorcontrib>Sun, Kang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>https://resources.nclive.org/materials</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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The passage of maternal glucocorticoids into the fetal circulation is governed by 11beta-Hydroxysteroid Dehydrogenase Type 2 (HSD11B2) in the placental syncytiotrophoblasts. Human chorionic gonadotropin (hCG) plays an important role in maintaining placental HSD11B2 expression via activation of the cAMP pathway. In this study, we investigated the relationship between the activation of the cAMP pathway by hCG and subsequent phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) or p38 mitogen-activated protein kinase (MAPK) pathways in the regulation of placental HSD11B2 expression in human placental syncytiotrophoblasts. We found that treatment of the placental syncytiotrophoblasts with either hCG or dibutyl cAMP (dbcAMP) could promote the phosphorylation of p38 and ERK1/2. Inhibition of p38 MAPK with SB203580 not only reduced the basal HSD11B2 mRNA and protein levels but also attenuated HSD11B2 levels induced by either hCG or dbcAMP. By contrast, inhibition of ERK1/2 with PD98059 increased the basal mRNA and protein levels of HSD11B2 and had no effect on HSD11B2 mRNA and protein levels induced by either hCG or dbcAMP. These data suggest that p38 MAPK is involved in both basal and hCG/cAMP-induced expression of HSD11B2, and ERK1/2 may play a role opposite to p38 MAPK at least in the basal expression of HSD11B2 in human placental syncytiotrophoblasts and that there is complicated cross-talk between hCG/cAMP and MAPK cascades in the regulation of placental HSD11B2 expression.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25229504</pmid><doi>10.1371/journal.pone.0107938</doi><oa>free_for_read</oa></addata></record> |
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subjects | 11-beta-Hydroxysteroid Dehydrogenase Type 2 - biosynthesis 11β-Hydroxysteroid dehydrogenase Activation Apoptosis Binding sites Biology and Life Sciences Cascades Chorionic gonadotropin Chorionic Gonadotropin - pharmacology Chorionic gonadotropins Consent Cyclic AMP Cyclic AMP - chemistry Cyclic AMP - metabolism Cyclic AMP - pharmacology Dehydrogenases Enzyme Induction - drug effects Extracellular signal-regulated kinase Female Fetuses Gestation Glucocorticoids Glycoproteins Gonadotropins Hospitals Humans Inhibition Kinases Life sciences MAP kinase MAP Kinase Signaling System - drug effects Medicine and Health Sciences Mitogen-Activated Protein Kinases - metabolism mRNA Pathways Phosphorylation Phosphorylation - drug effects Pituitary (anterior) Placenta Pregnancy Protein kinase Proteins RNA Rodents Signal transduction Sp1 Transcription Factor - metabolism Trophoblasts Trophoblasts - cytology Trophoblasts - drug effects Trophoblasts - metabolism |
title | Cross-talk between cAMP and MAPK pathways in HSD11B2 induction by hCG in placental trophoblasts |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T08%3A32%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cross-talk%20between%20cAMP%20and%20MAPK%20pathways%20in%20HSD11B2%20induction%20by%20hCG%20in%20placental%20trophoblasts&rft.jtitle=PloS%20one&rft.au=Shu,%20Qun&rft.date=2014-09-17&rft.volume=9&rft.issue=9&rft.spage=e107938&rft.pages=e107938-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0107938&rft_dat=%3Cgale_plos_%3EA418424468%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1562655927&rft_id=info:pmid/25229504&rft_galeid=A418424468&rft_doaj_id=oai_doaj_org_article_0f8565735958413cbed8cf180eb13dec&rfr_iscdi=true |