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The review summarizes evidence that GnRHR2 is present and functional despite predicted coding errors, describes receptor localization across multiple human tissues, and compares GnRH2/GnRHR2 signaling selectivity with GnRH1/GnRHR1. It also compiles findings that GnRH2 analogues can exert anti-proliferative, pro-apoptotic, and/or anti-metastatic effects across several reproductive cancer types, supporting GnRH2 as an emerging therapeutic target.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/role-of-gonadotropin-releasing-hormone-2-and-its-receptor-in-human-reproductive-cancers-mini-review/326723/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/role-of-gonadotropin-releasing-hormone-2-and-its-receptor-in-human-reproductive-cancers-mini-review/326723.png","ImageObject",300,407,{"name":92,"@type":93},"Logic","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-05","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What are GnRH2 and GnRHR2, and why are they relevant to reproduction and cancer?","Question",{"text":112,"@type":113},"GnRH2 is a mammalian decapeptide and GnRHR2 is its cognate receptor. The review highlights their presence in human tissues and reproductive cancer cells, linking them to regulation of tumor-promoting processes and therapeutic potential.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does GnRHR2 signaling compare with GnRHR1 signaling?",{"text":117,"@type":113},"The review describes differences in binding affinity and activity between GnRH2/GnRHR2 and GnRH1/GnRHR1. Both receptors can utilize Gaq/11 to activate IP3 synthesis and PKC, but downstream pathways diverge, implying distinct physiological effects.",{"name":119,"@type":110,"acceptedAnswer":120},"What anti-cancer effects do GnRH2 analogues show in reproductive cancers?",{"text":121,"@type":113},"GnRH2 analogues are reported to have potent anti-proliferative, pro-apoptotic, and/or antimetastatic effects. The review notes these effects across multiple reproductive cancer types including endometrial, breast, placental, ovarian, and prostate.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},326723,1790013183,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},1099513958762,"https://ap-avatar.wpscdn.com/avatar/1000023916a998db790?x-image-process=image/resize,m_fixed,w_180,h_180&k=1784791008015729253","TYPE Mini Review  \nPUBLISHED 08 January 2024 DOI 10.3389/fendo.2023.1341162  \nOPEN ACCESS  \nEDITED BY  \nTatiana Fiordelisio,  \nNational Autonomous University of Mexico, Mexico  \nREVIEWED BY Rahul Pal,  \nNational Institute of Immunology (NII), India Payam Behzadi,  \nIslamic Azad University, ShahreQods, Iran  \n*CORRESPONDENCE Amy T. Desaulniers  \n [desaulniers@unl.edu](desaulniers@unl.edu)  \nRECEIVED 19 November 2023  \nACCEPTED 13 December 2023  \nPUBLISHED 08 January 2024  \nCITATION  \nDesaulniers AT and White BR (2024) Role of gonadotropin-releasing hormone 2 and its receptor in human reproductive cancers. Front. Endocrinol. 14:1341162 .  \ndoi: 10.3389/fendo.2023.1341162  \nCOPYRIGHT  \n© 2024 Desaulniers and White. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nRole of gonadotropin-releasing hormone 2 and its receptor inhuman reproductive cancers  \nAmy T. Desaulniers 1* and Brett R. White 2  \n1School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE, United States, 2 Department of Animal Science, University of Nebraska-Lincoln, Lincoln,  \nNE, United States  \nGonadotropin-releasing hormone (GnRH1) and its receptor (GnRHR1) drive reproduction by regulating gonadotropins. Another form, GnRH2, and its receptor (GnRHR2), also exist in mammals. In humans, GnRH2 and GnRHR2 genes are present, but coding errors in the GnRHR2 gene are predicted to hinder full-length protein production. Nonetheless, mounting evidence supports the presence of a functional GnRHR2 in humans. GnRH2 and its receptor have been identified throughout the body, including peripheral reproductive tissues like the ovary, uterus, breast, and prostate. In addition, GnRH2 and its receptor have been detected in a wide number of reproductive cancer cells in humans. Notably, GnRH2 analogues have potent anti-proliferative, pro-apoptotic, and/or antimetastatic effects on various reproductive cancers, including endometrial, breast, placental, ovarian, and prostate. Thus, GnRH2 is an emerging target to treat human reproductive cancers.  \nKEYWORDS  \nGnRH2, GnRHR2, reproductive cancer, breast, prostate, endometrial, ovarian, placental  \nIntroduction  \nGnRH2  \nHypothalamic GnRH1 binds GnRHR1 on gonadotropes, promoting gonadotropin [luteinizing hormone (LH) and follicle-stimulating hormone (FSH)] synthesis/secretion. Another form, GnRH2, is also present in mammals (1) . GnRH2 is ubiquitously expressed (1) and originates from the GnRH2 gene (chromosome 20) in humans (2) . Both decapeptides, GnRH2 and GnRH1 have a 70% sequence identity (3) . Amino acid substitutions in GnRH2 enhance its stability (4) and half-life (5, 6) compared with GnRH1 .  \nFrontiers in Endocrinology 01 [frontiersin.org](frontiersin.org)  \nGnRHR2  \nA 7-transmembrane (TM) G-protein coupled receptor (GPCR) specific to GnRHR2 is present in mammals and ubiquitously expressed (1) . GnRH2 binds its cognate receptor with greater affinity than GnRHR1 (24-fold increase (7)), leading to greater activity (up to 440-fold increase (8–10)) . In contrast, GnRH1 exhibits 12-fold greater activity at GnRHR1 compared to GnRH2 (9, 11) . Thus, GnRHR2 displays greater selectivity for GnRH2, whereas GnRHR1 binds/activates both decapeptides reasonably well (8) . Both receptors utilize Gaq/11 to trigger IP3 synthesis and activate protein kinase C (PKC (8, 12, 13)), but downstream signaling pathways diverge (7) . Additionally, GnRH2 activation of GnRHR1 initiates different signaling pathways than GnRH1 (14), suggesting that GnRH2 elicits different physiological effects than GnRH1 at GnRHR1 .  \nHumans mai","cbCaivHgebfX1CTM","https://ap.wps.com/l/cbCaivHgebfX1CTM","pdf",808356,"English","# Introduction\n## GnRH2\n## GnRHR2\n# GnRH2 and GnRHR2 in human reproductive cancers","[{\"question\":\"What are GnRH2 and GnRHR2, and why are they relevant to reproduction and cancer?\",\"answer\":\"GnRH2 is a mammalian decapeptide and GnRHR2 is its cognate receptor. The review highlights their presence in human tissues and reproductive cancer cells, linking them to regulation of tumor-promoting processes and therapeutic potential.\"},{\"question\":\"How does GnRHR2 signaling compare with GnRHR1 signaling?\",\"answer\":\"The review describes differences in binding affinity and activity between GnRH2/GnRHR2 and GnRH1/GnRHR1. Both receptors can utilize Gaq/11 to activate IP3 synthesis and PKC, but downstream pathways diverge, implying distinct physiological effects.\"},{\"question\":\"What anti-cancer effects do GnRH2 analogues show in reproductive cancers?\",\"answer\":\"GnRH2 analogues are reported to have potent anti-proliferative, pro-apoptotic, and/or antimetastatic effects. The review notes these effects across multiple reproductive cancer types including endometrial, breast, placental, ovarian, and prostate.\"}]","Role of gonadotropin-releasing hormone 2 and its receptor in human reproductive cancers - Mini Review | PDF",1789975193,25]