{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:11:42Z","timestamp":1786579902372,"version":"build-2736575974"},"reference-count":65,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031478","name":"NextGenerationEU","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Italian Ministry of University and Research","award":["PNRR - M4C2-I1.3"],"award-info":[{"award-number":["PNRR - M4C2-I1.3"]}]},{"name":"Italian Ministry of University and Research","award":["PE_00000019"],"award-info":[{"award-number":["PE_00000019"]}]},{"name":"Italian Ministry of University and Research","award":["CUP E93C22001860006"],"award-info":[{"award-number":["CUP E93C22001860006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>LH\/choriogonadotropin (hCG) receptor (LHCGR) and the G protein-coupled estrogen receptor (GPER) are coexpressed in the ovary and support reproduction. The latter is involved in pathophysiological conditions and has been suggested as a potential therapeutic target. However, its role is still controversial, and several studies reported GPER to form heterocomplexes with other class A G protein-coupled receptors, modulating their signaling cascades. We evaluated if GPER interacts with LHCGR and impacts ligand-mediated pathways. In HEK293, LHCGR-GPER heteromers allosterically modulate LH\/hCG-mediated signaling by preventing receptor coupling with Gq protein, leading to inhibition of phospholipase C pathway, and related transcriptional and mitogenic functions. This effect is prevented by mutant GPER unable to form heteromers with LHCGR. Interestingly, GPER expression has no effect on LH\/hCG-induced Gs\/cAMP\/protein kinase A pathway activation, demonstrating selective inhibition of Gq pathway. These results were not recapitulated in cells displaying insufficient endogenous Gq protein expression levels, whereas they are recovered under exogenous Gq overexpression. Our data strengthen the concept that GPER may act as a modulator of other membrane G protein-coupled receptors, and a potential new target for treatment of tumors displaying Gq signalling.<\/jats:p>","DOI":"10.1210\/endocr\/bqaf174","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T13:08:03Z","timestamp":1763644083000},"source":"Crossref","is-referenced-by-count":1,"title":["Heteromerization of G Protein-coupled Estrogen Receptor With the LH Receptor Biases G Protein Signaling"],"prefix":"10.1210","volume":"167","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4553-4191","authenticated-orcid":false,"given":"Clara","family":"Lazzaretti","sequence":"first","affiliation":[{"name":"Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Baggiovara Hospital , Modena 41126 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of Modena and Reggio Emilia, Baggiovara Hospital , Modena 41126 ,","place":["Italy"]},{"name":"International PhD School in Clinical and Experimental Medicine (CEM), University of Modena and Reggio Emilia , Modena 41125 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Baschieri","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Baggiovara Hospital , Modena 41126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Fusco","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Baggiovara Hospital , Modena 41126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"De Carlini","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Baggiovara Hospital , Modena 41126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Canu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathological Anatomy, Azienda USL\/Azienda Ospedaliero-Universitaria of Modena , Modena 41126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Varani","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathological Anatomy, Azienda USL\/Azienda Ospedaliero-Universitaria of Modena , Modena 41126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Nicoli","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Fertility Center, ASMN, Azienda Unit\u00e0 Sanitaria Locale-IRCCS di Reggio Emilia , Reggio Emilia 42123 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Morini","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Fertility Center, ASMN, Azienda Unit\u00e0 Sanitaria Locale-IRCCS di Reggio Emilia , Reggio Emilia 42123 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Villani","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Fertility Center, ASMN, Azienda Unit\u00e0 Sanitaria Locale-IRCCS di Reggio Emilia , Reggio Emilia 42123 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Fanelli","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia , Modena 41125 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Reiter","sequence":"additional","affiliation":[{"name":"Physiologie de la Reproduction et des Comportements (PRC), Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS), Institut Fran\u00e7ais du Cheval et de l'Equitation (IFCE), Universit\u00e9 de Tours , 37380 Nouzilly ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2133-4304","authenticated-orcid":false,"given":"Manuela","family":"Simoni","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Baggiovara Hospital , Modena 41126 ,","place":["Italy"]},{"name":"Center for Genomic Research, University of Modena and Reggio Emilia , Modena 41125 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