Inhibition of Human Type I Gonadotropin-Releasing Hormone Receptor (GnRHR) Function by Expression of a Human Type II GnRHR Gene Fragment | Endocrinology

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Pawson,Stuart Maudsley,Kevin Morgan,Lindsay Davidson,Zvi Naor,Robert P. Millar","issue_and_volume":"Volume 146 | Issue 6","type":"research-article","online_publication_date":"2005-06-01","access_type":"Paid","license_type":"free","event_type":"Login-full-text","supplier_tag":"SC_Journals","object_type":"Article","taxonomy":"taxId%3a39%7ctaxLabel%3aAcademicSubjects%7cnodeId%3aMED00010%7cnodeLabel%3aMedicine+and+Health%7cnodeLevel%3a1%3btaxId%3a39%7ctaxLabel%3aAcademicSubjects%7cnodeId%3aMED00160%7cnodeLabel%3aClinical+Medicine%7cnodeLevel%3a2%3btaxId%3a39%7ctaxLabel%3aAcademicSubjects%7cnodeId%3aMED00250%7cnodeLabel%3aEndocrinology+and+Diabetes%7cnodeLevel%3a3","siteid":"endo","authzrequired":"true","turnaway_id":"SUB_NONE","doi":"10.1210/en.2005-0133"}]; </script> <script> (function (w, d, s, l, i) { w[l] = w[l] || []; w[l].push({ 'gtm.start': new Date().getTime(), event: 'gtm.js' }); var f = d.getElementsByTagName(s)[0], j = d.createElement(s), dl = l != 'dataLayer' ? 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Humans possess only one functional GnRH receptor, the type I GnRH receptor (GnRHR-I). A type II GnRH receptor (GnRHR-II) gene homolog exists, but","pageStart":"2639","pageEnd":"2649","siteName":"OUP Academic","thumbnailURL":"https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/endo/146/6/10.1210_en.2005-0133/1/m_zee0060520890001.jpeg?Expires=1794510429&Signature=ycfrE6yWA67m1M5Kbtz~ibVmqq2K7P2g~hHXOGch9-OL29EGgFLnzLk~L9ccNCjr4N7xzbLxDUIlxKoUTAc0ULccJiIOW9zb4AW0~yDQNSYbxOZMhY5PDjm08F4A2775dsDKequ7WLRD5apf7fKHZAONwQeU3k8tqLAU7YsNATsUSTXx~l2~potiCotfzOtHEHIEGm0lxrtA3qxJYcqppEA2m3XhOzUgletxU36VVor9iTqwFW6IcDoSqO8F3BOaqipdRSipTmU1gdBGK8EKWmjr-9-Hm7zK4ZrHnAFju5O3udFy7kVJ1BjIv5aAk4UQhaSdCYnfsqdDc155za85pQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA","headline":"Inhibition of Human Type I Gonadotropin-Releasing Hormone Receptor (GnRHR) Function by Expression of a Human Type II GnRHR Gene Fragment","image":"https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/endo/146/6/10.1210_en.2005-0133/1/m_zee0060520890001.jpeg?Expires=1794510429&Signature=ycfrE6yWA67m1M5Kbtz~ibVmqq2K7P2g~hHXOGch9-OL29EGgFLnzLk~L9ccNCjr4N7xzbLxDUIlxKoUTAc0ULccJiIOW9zb4AW0~yDQNSYbxOZMhY5PDjm08F4A2775dsDKequ7WLRD5apf7fKHZAONwQeU3k8tqLAU7YsNATsUSTXx~l2~potiCotfzOtHEHIEGm0lxrtA3qxJYcqppEA2m3XhOzUgletxU36VVor9iTqwFW6IcDoSqO8F3BOaqipdRSipTmU1gdBGK8EKWmjr-9-Hm7zK4ZrHnAFju5O3udFy7kVJ1BjIv5aAk4UQhaSdCYnfsqdDc155za85pQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA","image:alt":"Nucleotide and deduced amino acid sequence of the human GnRHR-II. The full GnRHR-II sequence is shown. The position of the frame shift in exon 1 is indicated by the arrow and X. The premature stop codon in exon 2 is indicated in bold italics and asterisk. The putative translation start codon 117 bp downstream of the premature stop codon is indicated in bold. The encoded GnRHR-II-reliquum sequence is underlined."} </script> <meta property="og:site_name" content="OUP Academic" /> <meta property="og:title" content="Inhibition of Human Type I Gonadotropin-Releasing Hormone Receptor (GnRHR) Function by Expression of a Human Type II GnRHR Gene Fragment" /> <meta property="og:description" content="Abstract. Humans possess only one functional GnRH receptor, the type I GnRH receptor (GnRHR-I). 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Humans possess only one functional GnRH receptor, the type I GnRH receptor (GnRHR-I). 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class="journal-info__format-label">Journal Article</span> </div> <div class="widget-items"> <div class="title-wrap"> <h1 class="wi-article-title article-title-main accessible-content-title at-articleTitle"> Inhibition of Human Type I Gonadotropin-Releasing Hormone Receptor (GnRHR) Function by Expression of a Human Type II GnRHR Gene Fragment <i class='' title='' ></i> </h1> <a href="#no-access-message" class="get-access get-access-jumplink at-get-access-jumplink js-no-access-jumplink"> <span class="get-access-text">Get access</span> <img class='get-access-icon' src='/UI/app/svg/chevron-right-white.svg' alt='Arrow' aria-hidden='true'> </a> </div> <div class="wi-authors at-ArticleAuthors"> <div class="al-authors-list"> <span class="al-author-name-more js-flyout-wrap"> <button type="button" class="linked-name js-linked-name-trigger btn-as-link">Adam J. Pawson</button><span class='delimiter'>, </span> <span class="al-author-info-wrap arrow-up"> <div class="info-card-author authorInfo_OUP_Abstract_ArticleTop_Info_Widget"> <div class="name-role-wrap"> <div class="info-card-name"> Adam J. Pawson <span class="info-card-footnote"><span class="xrefLink" id="jumplink-cor1"></span><a href="javascript:;" reveal-id="cor1" data-open="cor1" class="link link-ref link-reveal xref-default"></a></span> </div> </div> <div class="info-card-affilitation"> <div class="aff"><span class="label title-label">1</span>Human Reproductive Sciences Unit, Medical Research Council, EH16 4SB Edinburgh, Scotland, United Kingdom</div> </div> <div class="info-author-correspondence"> <div content-id="cor1"><span class="label title-label">*</span>Address all correspondence and requests for reprints to: Dr. Adam J. Pawson, Human Reproductive Sciences Unit, Medical Research Council, The University of Edinburgh Chancellor’s Building, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, United Kingdom.</div> </div> <div class="info-card-search-label"> Search for other works by this author on: </div> <div class="info-card-search info-card-search-internal"> <a href="/endo/search-results?f_Authors=Adam+J.+Pawson" rel="nofollow">Oxford Academic</a> </div> <div class="info-card-search info-card-search-google"> <a href="http://scholar.google.com/scholar?q=author:%22Pawson Adam J.%22">Google Scholar</a> </div> </div> </span> </span> <span class="al-author-name-more js-flyout-wrap"> <button type="button" class="linked-name js-linked-name-trigger btn-as-link">Stuart Maudsley</button><span class='delimiter'>, </span> <span class="al-author-info-wrap arrow-up"> <div class="info-card-author authorInfo_OUP_Abstract_ArticleTop_Info_Widget"> <div class="name-role-wrap"> <div class="info-card-name"> Stuart Maudsley </div> </div> <div class="info-card-affilitation"> <div class="aff"><span class="label title-label">1</span>Human Reproductive Sciences Unit, Medical Research Council, EH16 4SB Edinburgh, Scotland, United Kingdom</div> </div> <div class="info-card-search-label"> Search for other works by this author on: </div> <div class="info-card-search info-card-search-internal"> <a href="/endo/search-results?f_Authors=Stuart+Maudsley" rel="nofollow">Oxford Academic</a> </div> <div class="info-card-search info-card-search-google"> <a href="http://scholar.google.com/scholar?q=author:%22Maudsley Stuart%22">Google Scholar</a> </div> </div> </span> </span> <span class="al-author-name-more js-flyout-wrap"> <button type="button" class="linked-name js-linked-name-trigger btn-as-link">Kevin Morgan</button><span class='delimiter'>, </span> <span class="al-author-info-wrap arrow-up"> <div class="info-card-author authorInfo_OUP_Abstract_ArticleTop_Info_Widget"> <div class="name-role-wrap"> <div class="info-card-name"> Kevin Morgan </div> </div> <div class="info-card-affilitation"> <div class="aff"><span class="label title-label">1</span>Human Reproductive Sciences Unit, Medical Research Council, EH16 4SB Edinburgh, Scotland, United Kingdom</div> </div> <div class="info-card-search-label"> Search for other works by this author on: </div> <div class="info-card-search info-card-search-internal"> <a href="/endo/search-results?f_Authors=Kevin+Morgan" rel="nofollow">Oxford Academic</a> </div> <div class="info-card-search info-card-search-google"> <a href="http://scholar.google.com/scholar?q=author:%22Morgan Kevin%22">Google Scholar</a> </div> </div> </span> </span> <span class="al-author-name-more js-flyout-wrap"> <button type="button" class="linked-name js-linked-name-trigger btn-as-link">Lindsay Davidson</button><span class='delimiter'>, </span> <span class="al-author-info-wrap arrow-up"> <div class="info-card-author authorInfo_OUP_Abstract_ArticleTop_Info_Widget"> <div class="name-role-wrap"> <div class="info-card-name"> Lindsay Davidson </div> </div> <div class="info-card-affilitation"> <div class="aff"><span class="label title-label">1</span>Human Reproductive Sciences Unit, Medical Research Council, EH16 4SB Edinburgh, Scotland, United Kingdom</div> </div> <div class="info-card-search-label"> Search for other works by this author on: </div> <div class="info-card-search info-card-search-internal"> <a href="/endo/search-results?f_Authors=Lindsay+Davidson" rel="nofollow">Oxford Academic</a> </div> <div class="info-card-search info-card-search-google"> <a href="http://scholar.google.com/scholar?q=author:%22Davidson Lindsay%22">Google Scholar</a> </div> </div> </span> </span> <span class="al-author-name-more js-flyout-wrap"> <button type="button" class="linked-name js-linked-name-trigger btn-as-link">Zvi Naor</button><span class='delimiter'>, </span> <span class="al-author-info-wrap arrow-up"> <div class="info-card-author authorInfo_OUP_Abstract_ArticleTop_Info_Widget"> <div class="name-role-wrap"> <div class="info-card-name"> Zvi Naor </div> </div> <div class="info-card-affilitation"> <div class="aff"><span class="label title-label">1</span>Human Reproductive Sciences Unit, Medical Research Council, EH16 4SB Edinburgh, Scotland, United Kingdom</div> </div> <div class="info-card-search-label"> Search for other works by this author on: </div> <div class="info-card-search info-card-search-internal"> <a href="/endo/search-results?f_Authors=Zvi+Naor" rel="nofollow">Oxford Academic</a> </div> <div class="info-card-search info-card-search-google"> <a href="http://scholar.google.com/scholar?q=author:%22Naor Zvi%22">Google Scholar</a> </div> </div> </span> </span> <span class="al-author-name-more js-flyout-wrap"> <button type="button" class="linked-name js-linked-name-trigger btn-as-link">Robert P. Millar</button><span class='delimiter'></span> <span class="al-author-info-wrap arrow-up"> <div class="info-card-author authorInfo_OUP_Abstract_ArticleTop_Info_Widget"> <div class="name-role-wrap"> <div class="info-card-name"> Robert P. Millar </div> </div> <div class="info-card-affilitation"> <div class="aff"><span class="label title-label">1</span>Human Reproductive Sciences Unit, Medical Research Council, EH16 4SB Edinburgh, Scotland, United Kingdom</div> </div> <div class="info-card-search-label"> Search for other works by this author on: </div> <div class="info-card-search info-card-search-internal"> <a href="/endo/search-results?f_Authors=Robert+P.+Millar" rel="nofollow">Oxford Academic</a> </div> <div class="info-card-search info-card-search-google"> <a href="http://scholar.google.com/scholar?q=author:%22Millar Robert P.%22">Google Scholar</a> </div> </div> </span> </span> </div> </div> <div class="pub-history-wrap clearfix js-history-dropdown-wrap"> <div class="pub-history-row clearfix"> <div class="ww-citation-primary"><em>Endocrinology</em>, Volume 146, Issue 6, 1 June 2005, Pages 2639–2649, <a href='https://doi.org/10.1210/en.2005-0133'>https://doi.org/10.1210/en.2005-0133</a></div> </div> <div class="pub-history-row clearfix"> <div class="ww-citation-date-wrap"> <div class="citation-label">Published:</div> <div class="citation-date">01 June 2005</div> </div> <a href="javascript:;" class="history-label js-history-dropdown-trigger st-article-history at-ArticleHistory"> <span>Article history</span><i class="icon-general-arrow-filled-down arrow-icon"></i> </a> </div> <div class="ww-history js-history-entries-wrap at-history-entries-wrap"> <div class="history-entry at-history-entry"> <div class="wi-state">Received:</div> <div class="wi-date">03 February 2005</div> </div> <div class="history-entry at-history-entry"> <div class="wi-state">Accepted:</div> <div class="wi-date">28 February 2005</div> </div> <div class="history-entry at-history-entry"> <div class="wi-state">Published:</div> <div class="wi-date">01 June 2005</div> </div> </div> </div> </div> </div> <script> $(document).ready(function () { $('.article-top-widget').on('click', '.ati-toggle-trigger', function () { $(this).find('.icon-general-add, .icon-minus').toggleClass('icon-minus icon-general-add'); $(this).siblings('.ati-toggle-content').toggleClass('hide'); }); // In Chrome, an anchor tag with target="_blank" and a "mailto:" href opens a new tab/window as well as the email client // I suspect this behavior will be corrected in the future // Remove the target="_blank" $('ul.wi-affiliationList').find('a[href^="mailto:"]').each(function () { $(this).removeAttr('target'); }); }); </script> </div> <div class="widget widget-ArticleLinks widget-instance-OUP_Article_Links_Widget"> </div> <div class="article-body js-content-body"> <div class="toolbar-wrap js-toolbar-wrap"> <div class="toolbar-inner-wrap"> <ul id="Toolbar" role="navigation"> <li class="toolbar-item item-with-dropdown item-views"> <a class="at-views-dropdown drop-trigger" href="javascript:;" data-dropdown="FilterDrop" aria-haspopup="true"> <i class="icon-menu_views"></i> <div class="toolbar-label"> <div class="toolbar-text">Views</div> <i class="icon-general-arrow-filled-down arrow-icon"></i> </div> </a> <ul id="ViewsDrop" class="f-dropdown js-dropdown-content" data-dropdown-content aria-label="submenu"> <div class="arrow-up"></div> <li class="article-content-filter js-article-content-filter" data-content-filter="article-content"> <a href="javascript:;"><span>Article contents</span></a> </li> <li class="at-figures-tables article-content-filter js-article-content-filter" data-content-filter="figures-tables"> <a href="javascript:;"><span>Figures & tables</span></a> </li> <li class="article-content-filter js-article-content-filter" data-content-filter="video"> <a href="javascript:;"><span>Video</span></a> </li> <li class="article-content-filter js-article-content-filter" data-content-filter="audio"> <a href="javascript:;"><span>Audio</span></a> </li> <li class="article-content-filter js-article-content-filter" data-content-filter="supplementary-data"> <a href="javascript:;"><span>Supplementary Data</span></a> </li> </ul> </li> <li class="toolbar-item item-cite js-item-cite"> <div class="widget widget-ToolboxGetCitation widget-instance-OUP_Get_Citation"> <a href="#" class="js-cite-button at-CiteButton" data-reveal-id="getCitation" data-reveal> <i class="icon-read-more"></i> <span>Cite</span> </a> <div id="getCitation" class="reveal-modal js-citation-modal" data-reveal> <h3 class="modal-title">Cite</h3> <div class="oxford-citation-text"> <p>Adam J. 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A type II GnRH receptor (GnRHR-II) gene homolog exists, but it is disrupted by a frame shift and premature stop codon, suggesting that a conventional receptor is not translated from this gene. However, the gene remains transcriptionally active and displays alternative splicing. We identified a putative translational start site 117 bp downstream of the premature stop codon. Use of this start codon encodes a protein (designated as the GnRHR-II-reliquum) corresponding to the domains from the cytoplasmic end of transmembrane domain-5 to the carboxyl terminus of the putative full-length receptor. Immunocytochemistry revealed that GnRHR-II-reliquum expression appeared to be localized throughout the cytoplasm. Transient cotransfection of GnRHR-I and GnRHR-II-reliquum constructs into COS-7 cells resulted in reduced expression of the GnRHR-I at the cell surface and impaired signaling via the GnRHR-I as revealed by reduction of GnRH-induced inositol phosphate accumulation. This inhibitory effect was specific and dependent on the degree of GnRHR-II-reliquum coexpressed. Immunoblot analysis revealed that the total cell GnRHR-I complement, <em>i.e</em>. both cell-surface and nascent intracellular receptors, was markedly reduced by coexpression of the GnRHR-II-reliquum. Treatments with cell-permeable agents that blocked either <em>de novo</em> protein synthesis (cycloheximide) or proteinase-mediated degradation (leupeptin and phenylmethylsulfonyl fluoride) failed to alter the inhibitory effect of GnRHR-II-reliquum coexpression, suggesting that the inhibitory effect is exerted at the nucleus/endoplasmic reticulum or Golgi apparatus level, possibly by perturbing normal processing of GnRHR-I from these sites. We suggest that the GnRHR-II-reliquum plays a modulatory role in GnRHR-I expression.</p></section> <div class="article-metadata-panel clearfix at-ArticleMetadata"></div>  <div class="widget widget-ArticlePubStateInfo widget-instance-OUP_ArticlePubStateInfo"> </div> <div class="article-metadata-standalone-panel clearfix"></div> <div class="copyright copyright-statement">Copyright © 2005 by The Endocrine Society</div> <span id="UserHasAccess" data-userHasAccess="False"></span> </div> </div> </div> <div class="widget widget-SolrResourceMetadata widget-instance-OUP_Article_ResourceMetadata_Widget"> <div class="article-metadata-panel solr-resource-metadata js-metadata-panel at-ContentMetadata"> <div class="article-metadata-tocSections"> <div class="article-metadata-tocSections-title">Issue Section:</div> <a href="/endo/search-results?f_TocHeadingTitleList=Receptors">Receptors</a> </div> </div> </div> <div class="widget widget-EditorInformation 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Inhibition of Human Type I Gonadotropin-Releasing Hormone Receptor (GnRHR) Function by Expression of a Human Type II GnRHR Gene Fragment | Endocrinology | Oxford Academic