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Nuclear Progesterone Receptors in the Human Pregnancy Myometrium: Evidence that Parturition Involves Functional Progesterone Withdrawal Mediated by Increased Expression of Progesterone Receptor-A
Context: We examined whether human parturition involves functional progesterone withdrawal mediated by changes in myometrial expression of progesterone receptors (PRs)-A and -B. Objective: Our objectives were to: 1) measure PR-A and PR-B protein levels in human pregnancy myometrium and determine whe...
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| Published in: | The journal of clinical endocrinology and metabolism 2007-05, Vol.92 (5), p.1927-1933 |
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| Main Authors: | , , , , , , |
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| container_end_page | 1933 |
| container_issue | 5 |
| container_start_page | 1927 |
| container_title | The journal of clinical endocrinology and metabolism |
| container_volume | 92 |
| creator | Merlino, Amy A. Welsh, Toni N. Tan, Huiqing Yi, Li Juan Cannon, Vernon Mercer, Brian M. Mesiano, Sam |
| description | Context: We examined whether human parturition involves functional progesterone withdrawal mediated by changes in myometrial expression of progesterone receptors (PRs)-A and -B.
Objective: Our objectives were to: 1) measure PR-A and PR-B protein levels in human pregnancy myometrium and determine whether the PR-A to PR-B ratio changes with advancing gestation and labor onset; and 2) determine how changes in the PR-A to PR-B ratio affect myometrial cell progesterone responsiveness.
Design: PR protein levels and cellular localization were measured by Western blotting and immunohistochemistry, respectively, in lower uterine segment uterine wall tissue from preterm ( |
| doi_str_mv | 10.1210/jc.2007-0077 |
| format | article |
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Objective: Our objectives were to: 1) measure PR-A and PR-B protein levels in human pregnancy myometrium and determine whether the PR-A to PR-B ratio changes with advancing gestation and labor onset; and 2) determine how changes in the PR-A to PR-B ratio affect myometrial cell progesterone responsiveness.
Design: PR protein levels and cellular localization were measured by Western blotting and immunohistochemistry, respectively, in lower uterine segment uterine wall tissue from preterm (<37 wk; not laboring; n = 5) and term (37–40 wk; not in labor: n = 6; in labor: n = 5) cesarean delivery. The capacity for PR-A and PR-B, alone and in combination, to mediate genomic progesterone responsiveness measured by the activity of a progesterone-responsive reporter plasmid was examined by artificially modulating their levels in the PHM1–31 myometrial cell line.
Results: PR-A and PR-B immunostaining was detected only in the nucleus of myometrial cells. The PR-A to PR-B protein ratio was 0.49 ± 0.082 (mean ± sem) in preterm tissue; increased to 1.03 ± 0.071 (P < 0.001) in nonlaboring term tissue; and increased further to 2.65 ± 0.344 (P < 0.001) in laboring term tissue. Only PR-B mediated progesterone-induced transcriptional activity. PR-A had no effect alone but markedly decreased PR-B-mediated progesterone responsiveness.
Conclusions: Functional progesterone withdrawal in human parturition may be mediated by an increase in the myometrial PR-A to PR-B ratio due to increased PR-A expression.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2007-0077</identifier><identifier>PMID: 17341556</identifier><identifier>CODEN: JCEMAZ</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Adult ; Biological and medical sciences ; Blotting, Western ; Cell Line ; Cell Nucleus - metabolism ; Endocrinopathies ; Female ; Fundamental and applied biological sciences. Psychology ; Humans ; Immunohistochemistry ; Medical sciences ; Myometrium - cytology ; Myometrium - metabolism ; Parturition - physiology ; Plasmids - genetics ; Pregnancy - metabolism ; Progesterone - physiology ; Receptors, Cytoplasmic and Nuclear - metabolism ; Receptors, Progesterone - biosynthesis ; RNA, Small Interfering - genetics ; Transfection ; Vertebrates: endocrinology</subject><ispartof>The journal of clinical endocrinology and metabolism, 2007-05, Vol.92 (5), p.1927-1933</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c401t-940089007b1cc8d649962cd3a9998d00638cb5538417d8a93568c7b6c03a139e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18747231$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17341556$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Merlino, Amy A.</creatorcontrib><creatorcontrib>Welsh, Toni N.</creatorcontrib><creatorcontrib>Tan, Huiqing</creatorcontrib><creatorcontrib>Yi, Li Juan</creatorcontrib><creatorcontrib>Cannon, Vernon</creatorcontrib><creatorcontrib>Mercer, Brian M.</creatorcontrib><creatorcontrib>Mesiano, Sam</creatorcontrib><title>Nuclear Progesterone Receptors in the Human Pregnancy Myometrium: Evidence that Parturition Involves Functional Progesterone Withdrawal Mediated by Increased Expression of Progesterone Receptor-A</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Context: We examined whether human parturition involves functional progesterone withdrawal mediated by changes in myometrial expression of progesterone receptors (PRs)-A and -B.
Objective: Our objectives were to: 1) measure PR-A and PR-B protein levels in human pregnancy myometrium and determine whether the PR-A to PR-B ratio changes with advancing gestation and labor onset; and 2) determine how changes in the PR-A to PR-B ratio affect myometrial cell progesterone responsiveness.
Design: PR protein levels and cellular localization were measured by Western blotting and immunohistochemistry, respectively, in lower uterine segment uterine wall tissue from preterm (<37 wk; not laboring; n = 5) and term (37–40 wk; not in labor: n = 6; in labor: n = 5) cesarean delivery. The capacity for PR-A and PR-B, alone and in combination, to mediate genomic progesterone responsiveness measured by the activity of a progesterone-responsive reporter plasmid was examined by artificially modulating their levels in the PHM1–31 myometrial cell line.
Results: PR-A and PR-B immunostaining was detected only in the nucleus of myometrial cells. The PR-A to PR-B protein ratio was 0.49 ± 0.082 (mean ± sem) in preterm tissue; increased to 1.03 ± 0.071 (P < 0.001) in nonlaboring term tissue; and increased further to 2.65 ± 0.344 (P < 0.001) in laboring term tissue. Only PR-B mediated progesterone-induced transcriptional activity. PR-A had no effect alone but markedly decreased PR-B-mediated progesterone responsiveness.
Conclusions: Functional progesterone withdrawal in human parturition may be mediated by an increase in the myometrial PR-A to PR-B ratio due to increased PR-A expression.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cell Line</subject><subject>Cell Nucleus - metabolism</subject><subject>Endocrinopathies</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Medical sciences</subject><subject>Myometrium - cytology</subject><subject>Myometrium - metabolism</subject><subject>Parturition - physiology</subject><subject>Plasmids - genetics</subject><subject>Pregnancy - metabolism</subject><subject>Progesterone - physiology</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>Receptors, Progesterone - biosynthesis</subject><subject>RNA, Small Interfering - genetics</subject><subject>Transfection</subject><subject>Vertebrates: endocrinology</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNptkUFv1DAQhS0Eokvhxhn5AidS7NiJbW5VtaWVWqgQCG6RY8-2XiX21nYW9vfxx3DYlSqkHqyRR9-8Gb2H0GtKTmhNyYe1OakJEVV54glaUMWbSlAlnqIFITWtlKh_HqEXKa0JoZw37Dk6ooJx2jTtAv35PJkBdMQ3MdxCyhCDB_wVDGxyiAk7j_Md4Itp1L4wcOu1Nzt8vQsj5Oim8SNebp0Fb6CAOuMbHfMUXXbB40u_DcMWEj6fvJk7evh_zw-X72zUv0r_GqzTGSzud2XORNCpfJa_NxFSmsXC6vEbq9OX6NlKDwleHeox-n6-_HZ2UV19-XR5dnpVGU5orhQnRKpiU0-NkbblSrW1sUwrpaQlpGXS9E3DJKfCSq1Y00oj-tYQpilTwI7Ru73uJob7qRzSjS4ZGAbtIUypE4S3DZd1Ad_vQRNDShFW3Sa6UcddR0k3h9atTTeH1s2hFfzNQXfqR7AP8CGlArw9ADoZPaxiycClB04KLmpGC8f2HHgbTHQe_rnXrcMUi_fp8fV_AYlktH0</recordid><startdate>20070501</startdate><enddate>20070501</enddate><creator>Merlino, Amy A.</creator><creator>Welsh, Toni N.</creator><creator>Tan, Huiqing</creator><creator>Yi, Li Juan</creator><creator>Cannon, Vernon</creator><creator>Mercer, Brian M.</creator><creator>Mesiano, Sam</creator><general>Endocrine Society</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>7X8</scope></search><sort><creationdate>20070501</creationdate><title>Nuclear Progesterone Receptors in the Human Pregnancy Myometrium: Evidence that Parturition Involves Functional Progesterone Withdrawal Mediated by Increased Expression of Progesterone Receptor-A</title><author>Merlino, Amy A. ; Welsh, Toni N. ; Tan, Huiqing ; Yi, Li Juan ; Cannon, Vernon ; Mercer, Brian M. ; Mesiano, Sam</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c401t-940089007b1cc8d649962cd3a9998d00638cb5538417d8a93568c7b6c03a139e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Cell Line</topic><topic>Cell Nucleus - metabolism</topic><topic>Endocrinopathies</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Medical sciences</topic><topic>Myometrium - cytology</topic><topic>Myometrium - metabolism</topic><topic>Parturition - physiology</topic><topic>Plasmids - genetics</topic><topic>Pregnancy - metabolism</topic><topic>Progesterone - physiology</topic><topic>Receptors, Cytoplasmic and Nuclear - metabolism</topic><topic>Receptors, Progesterone - biosynthesis</topic><topic>RNA, Small Interfering - genetics</topic><topic>Transfection</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Merlino, Amy A.</creatorcontrib><creatorcontrib>Welsh, Toni N.</creatorcontrib><creatorcontrib>Tan, Huiqing</creatorcontrib><creatorcontrib>Yi, Li Juan</creatorcontrib><creatorcontrib>Cannon, Vernon</creatorcontrib><creatorcontrib>Mercer, Brian M.</creatorcontrib><creatorcontrib>Mesiano, Sam</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>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Merlino, Amy A.</au><au>Welsh, Toni N.</au><au>Tan, Huiqing</au><au>Yi, Li Juan</au><au>Cannon, Vernon</au><au>Mercer, Brian M.</au><au>Mesiano, Sam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nuclear Progesterone Receptors in the Human Pregnancy Myometrium: Evidence that Parturition Involves Functional Progesterone Withdrawal Mediated by Increased Expression of Progesterone Receptor-A</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2007-05-01</date><risdate>2007</risdate><volume>92</volume><issue>5</issue><spage>1927</spage><epage>1933</epage><pages>1927-1933</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><coden>JCEMAZ</coden><abstract>Context: We examined whether human parturition involves functional progesterone withdrawal mediated by changes in myometrial expression of progesterone receptors (PRs)-A and -B.
Objective: Our objectives were to: 1) measure PR-A and PR-B protein levels in human pregnancy myometrium and determine whether the PR-A to PR-B ratio changes with advancing gestation and labor onset; and 2) determine how changes in the PR-A to PR-B ratio affect myometrial cell progesterone responsiveness.
Design: PR protein levels and cellular localization were measured by Western blotting and immunohistochemistry, respectively, in lower uterine segment uterine wall tissue from preterm (<37 wk; not laboring; n = 5) and term (37–40 wk; not in labor: n = 6; in labor: n = 5) cesarean delivery. The capacity for PR-A and PR-B, alone and in combination, to mediate genomic progesterone responsiveness measured by the activity of a progesterone-responsive reporter plasmid was examined by artificially modulating their levels in the PHM1–31 myometrial cell line.
Results: PR-A and PR-B immunostaining was detected only in the nucleus of myometrial cells. The PR-A to PR-B protein ratio was 0.49 ± 0.082 (mean ± sem) in preterm tissue; increased to 1.03 ± 0.071 (P < 0.001) in nonlaboring term tissue; and increased further to 2.65 ± 0.344 (P < 0.001) in laboring term tissue. Only PR-B mediated progesterone-induced transcriptional activity. PR-A had no effect alone but markedly decreased PR-B-mediated progesterone responsiveness.
Conclusions: Functional progesterone withdrawal in human parturition may be mediated by an increase in the myometrial PR-A to PR-B ratio due to increased PR-A expression.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>17341556</pmid><doi>10.1210/jc.2007-0077</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0021-972X |
| ispartof | The journal of clinical endocrinology and metabolism, 2007-05, Vol.92 (5), p.1927-1933 |
| issn | 0021-972X 1945-7197 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70465482 |
| source | Oxford Journals Online |
| subjects | Adult Biological and medical sciences Blotting, Western Cell Line Cell Nucleus - metabolism Endocrinopathies Female Fundamental and applied biological sciences. Psychology Humans Immunohistochemistry Medical sciences Myometrium - cytology Myometrium - metabolism Parturition - physiology Plasmids - genetics Pregnancy - metabolism Progesterone - physiology Receptors, Cytoplasmic and Nuclear - metabolism Receptors, Progesterone - biosynthesis RNA, Small Interfering - genetics Transfection Vertebrates: endocrinology |
| title | Nuclear Progesterone Receptors in the Human Pregnancy Myometrium: Evidence that Parturition Involves Functional Progesterone Withdrawal Mediated by Increased Expression of Progesterone Receptor-A |
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