{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:53:22Z","timestamp":1782867202456,"version":"3.54.5"},"reference-count":154,"publisher":"The Royal Society","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Strathclyde Student Excellence Award (SEA) Studentship","award":["3569"],"award-info":[{"award-number":["3569"]}]},{"name":"University of Strathclyde Student Excellence Award (SEA) Studentship","award":["IY297BVBCY"],"award-info":[{"award-number":["IY297BVBCY"]}]},{"name":"University of Strathclyde Student Excellence Award (SEA) Studentship","award":["BH297BUZO8"],"award-info":[{"award-number":["BH297BUZO8"]}]},{"name":"University of Strathclyde Student Excellence Award (SEA) Studentship","award":["GB297BV6ZP"],"award-info":[{"award-number":["GB297BV6ZP"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Gonadotropin-releasing hormone (GnRH) is a peptide hormone forming a central component of the hypothalamic\u2013pituitary\u2013gonadal axis and is critical for controlling reproductive functions. Dysregulated GnRH is implicated in many steroid hormone-dependent diseases, and its receptor, GnRHR, is an attractive and clinically exploited therapeutic target. Mounting evidence suggests that beyond the hypothalamus and pituitary, GnRH and GnRHR are expressed in reproductive and non-reproductive, healthy and malignant peripheral tissues, where they act in an autocrine and paracrine manner. This review provides an updated overview of GnRH and GnRHR signalling with a focus on extrapituitary autocrine and paracrine roles in female reproductive health. We examine the molecular and cellular mechanisms of extrapituitary GnRHR signalling, including G-protein coupling profiles, and alternative cell-specific mechanisms that differ from pituitary signalling. We highlight recent data surrounding the (patho) physiological functions of local GnRH systems, including in the endometrium, ovary, placenta and breast, and their implications for hormone-dependent gynaecological conditions and cancers. Finally, we consider implications of peripheral GnRH\/GnRHR systems for therapeutic innovation, including avenues for targeted or biased GnRH-based therapeutics, GnRH\/GnRHR-mediated \u2018off target\u2019 effects of GnRH analogues, and explore future translational avenues for the treatment of both hormone-dependent and hormone-refractory diseases.<\/jats:p>","DOI":"10.1098\/rsob.260006","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:08:59Z","timestamp":1782864539000},"source":"Crossref","is-referenced-by-count":0,"title":["Understanding GnRH: local systems, signalling mechanisms and implications in female health"],"prefix":"10.1098","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8414-5935","authenticated-orcid":false,"given":"Lily","family":"Tosh","sequence":"first","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde 1 , Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7954-0742","authenticated-orcid":false,"given":"Kirsty","family":"Tinto","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde 1 , Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde 1 , Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Mulheran","sequence":"additional","affiliation":[{"name":"Chemical and Process Engineering, University of Strathclyde 2 , Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Ferro","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde 1 , Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"2026063020085293800_RSOB260006C1","first-page":"83","article-title":"Clinical applications of gonadotropin-releasing hormone analogues: a broad impact on reproductive medicine","volume":"4","author":"Saleh","year":"2023","journal-title":"F S Rep."},{"key":"2026063020085293800_RSOB260006C2","first-page":"31","article-title":"GnRH pulses\u2013the regulators of human reproduction","volume":"104","author":"Marshall","year":"1993","journal-title":"Trans. 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