{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:30:45Z","timestamp":1791419445050,"version":"4.3.3"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,6,19]]},"abstract":"<jats:p>\n                    The G protein-coupled receptor GPR54 (AXOR12, OT7T175) is central to acquisition of reproductive competency in mammals. Peptide ligands (kisspeptins) for this receptor are encoded by the\n                    <jats:italic>Kiss1<\/jats:italic>\n                    gene, and administration of exogenous kisspeptins stimulates hypothalamic gonadotropin-releasing hormone (GnRH) release in several species, including humans. To establish that kisspeptins are the authentic agonists of GPR54\n                    <jats:italic>in vivo<\/jats:italic>\n                    and to determine whether these ligands have additional physiological functions we have generated mice with a targeted disruption of the\n                    <jats:italic>Kiss1<\/jats:italic>\n                    gene.\n                    <jats:italic>Kiss1<\/jats:italic>\n                    -null mice are viable and healthy with no apparent abnormalities but fail to undergo sexual maturation. Mutant female mice do not progress through the estrous cycle, have thread-like uteri and small ovaries, and do not produce mature Graffian follicles. Mutant males have small testes, and spermatogenesis arrests mainly at the early haploid spermatid stage. Both sexes have low circulating gonadotropin (luteinizing hormone and follicle-stimulating hormone) and sex steroid (\u03b2-estradiol or testosterone) hormone levels. Migration of GnRH neurons into the hypothalamus appears normal with appropriate axonal connections to the median eminence and total GnRH content. The hypothalamic\u2013pituitary axis is functional in these mice as shown by robust luteinizing hormone secretion after peripheral administration of kisspeptin. The virtually identical phenotype of\n                    <jats:italic>Gpr54<\/jats:italic>\n                    - and\n                    <jats:italic>Kiss1<\/jats:italic>\n                    -null mice provides direct proof that kisspeptins are the true physiological ligand for the GPR54 receptor\n                    <jats:italic>in vivo. Kiss1<\/jats:italic>\n                    also does not seem to play a vital role in any other physiological processes other than activation of the hypothalamic\u2013pituitary\u2013gonadal axis, and loss of\n                    <jats:italic>Kiss1<\/jats:italic>\n                    cannot be overcome by compensatory mechanisms.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0704114104","type":"journal-article","created":{"date-parts":[[2007,6,12]],"date-time":"2007-06-12T16:22:58Z","timestamp":1181665378000},"page":"10714-10719","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":537,"title":["Hypogonadotropic hypogonadism in mice lacking a functional\n                    <i>Kiss1<\/i>\n                    gene"],"prefix":"10.1073","volume":"104","author":[{"given":"Xavier","family":"d'Anglemont de Tassigny","sequence":"first","affiliation":[{"name":"*Reproductive Physiology Group, Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge CB2 3EG, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Fagg","sequence":"additional","affiliation":[{"name":"*Reproductive Physiology Group, Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge CB2 3EG, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P. C.","family":"Dixon","sequence":"additional","affiliation":[{"name":"Paradigm Therapeutics Ltd. (now Takeda Cambridge Ltd.), 418 Cambridge Science Park, Milton Road, Cambridge CB4 0PA, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Day","sequence":"additional","affiliation":[{"name":"Paradigm Therapeutics Ltd. (now Takeda Cambridge Ltd.), 418 Cambridge Science Park, Milton Road, Cambridge CB4 0PA, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry G.","family":"Leitch","sequence":"additional","affiliation":[{"name":"*Reproductive Physiology Group, Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge CB2 3EG, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan G.","family":"Hendrick","sequence":"additional","affiliation":[{"name":"Paradigm Therapeutics Ltd. (now Takeda Cambridge Ltd.), 418 Cambridge Science Park, Milton Road, Cambridge CB4 0PA, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Zahn","sequence":"additional","affiliation":[{"name":"Paradigm Therapeutics Ltd. (now Takeda Cambridge Ltd.), 418 Cambridge Science Park, Milton Road, Cambridge CB4 0PA, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Franceschini","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Physiologie de la Reproduction et des Comportements, Unit\u00e9 Mixte de Recherche 6175, Institut National de la Recherche Agronomique\/Centre National de la Recherche Scientifique\/Universit\u00e9 Tours, 37380 Nouzilly, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Caraty","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Physiologie de la Reproduction et des Comportements, Unit\u00e9 Mixte de Recherche 6175, Institut National de la Recherche Agronomique\/Centre National de la Recherche Scientifique\/Universit\u00e9 Tours, 37380 Nouzilly, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark B. L.","family":"Carlton","sequence":"additional","affiliation":[{"name":"Paradigm Therapeutics Ltd. (now Takeda Cambridge Ltd.), 418 Cambridge Science Park, Milton Road, Cambridge CB4 0PA, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel A. J. R.","family":"Aparicio","sequence":"additional","affiliation":[{"name":"BC Cancer Agency, 675 West Tenth Avenue, Vancouver, BC, Canada V5Z 1LR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H.","family":"Colledge","sequence":"additional","affiliation":[{"name":"*Reproductive Physiology Group, Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge CB2 3EG, United 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