{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:21:22Z","timestamp":1791264082120,"version":"4.1.0"},"reference-count":33,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The neuropeptide RFamide-related peptide 3 (RFRP-3) has been implicated in the control of gonadotropin secretion in both birds and mammals. However, in mammals, depending on species, sex and photoperiod, inhibitory, excitatory, or no effect of RFRP-3 on the plasma concentration of LH has been reported. In the ewe, treatment with RFRP-3 either reduced LH concentration or had no effect, and treatment with an RFRP-3 receptor antagonist (ie, RF9) resulted in increased concentration of plasma LH. To clarify these conflicting results in the present study, a set of experiments was performed in ewes. Multiple iv injections of RFRP-3 (6 \u00d7 50 \u03bcg) in ovariectomized ewes had no effect on plasma LH pulsatility. In intact ewes a bolus injection (500 \u03bcg) or an injection (250, 500, or 1000 \u03bcg) followed by a 4-hour perfusion (250, 500, or 1000 \u03bcg \u00b7 h\u22121) of RFRP-3 had no effect on the LH pulse induced by kisspeptin (6.5 \u03bcg). In ovariectomized, estrogen-replaced ewes, the LH surge induced by estradiol benzoate was not modified by a 24-hour perfusion of RFRP-3 (500 \u03bcg h\u22121). Finally, although treatment with RF9 induced a robust release of LH, treatment with a more selective RFRP-3 receptor antagonist, GJ14, resulted in no evident increase of LH. In contrast to the inhibitory effect previously suggested, our data are more consistent with the concept that RFRP-3 has no direct effect on LH secretion in ewes and that RF9 effect on LH release is likely not RFRP-3 receptor mediated. Hence, RFRP-3 probably has a minor role on the control of LH secretion in the ewe.<\/jats:p>","DOI":"10.1210\/en.2015-1854","type":"journal-article","created":{"date-parts":[[2016,2,10]],"date-time":"2016-02-10T18:38:52Z","timestamp":1455129532000},"page":"1566-1575","source":"Crossref","is-referenced-by-count":51,"title":["No Evidence That RFamide-Related Peptide 3 Directly Modulates LH Secretion in the Ewe"],"prefix":"10.1210","volume":"157","author":[{"given":"C.","family":"Decourt","sequence":"first","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche Physiologie de la Reproduction et des Comportements (Institut National de la Recherche Agronomique, Unit\u00e9 Mixte de Recherche 85; Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 7247 Universit\u00e9 Fran\u00e7ois Rabelais Tours, IFCE) (C.D., K.A., V.R., D.L., J.B.-S., A.C., L.D., M.B.), F-37380 Nouzilly, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Anger","sequence":"first","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche Physiologie de la Reproduction et des Comportements (Institut National de la Recherche Agronomique, Unit\u00e9 Mixte de Recherche 85; Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 7247 Universit\u00e9 Fran\u00e7ois Rabelais Tours, IFCE) (C.D., K.A., V.R., D.L., J.B.-S., A.C., L.D., M.B.), F-37380 Nouzilly, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Robert","sequence":"first","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche Physiologie de la Reproduction et des Comportements (Institut National de la Recherche Agronomique, Unit\u00e9 Mixte de Recherche 85; Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 7247 Universit\u00e9 Fran\u00e7ois Rabelais Tours, IFCE) (C.D., K.A., V.R., D.L., J.B.-S., A.C., L.D., M.B.), F-37380 Nouzilly, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Lomet","sequence":"first","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche Physiologie de la Reproduction et des Comportements (Institut National de la Recherche Agronomique, Unit\u00e9 Mixte de Recherche 85; Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 7247 Universit\u00e9 Fran\u00e7ois Rabelais Tours, IFCE) (C.D., K.A., V.R., D.L., J.B.-S., A.C., L.D., M.B.), F-37380 Nouzilly, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Bartzen-Sprauer","sequence":"first","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche Physiologie de la Reproduction et des Comportements (Institut National de la Recherche Agronomique, Unit\u00e9 Mixte de Recherche 85; Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 7247 Universit\u00e9 Fran\u00e7ois Rabelais Tours, IFCE) (C.D., K.A., V.R., D.L., J.B.-S., A.C., L.D., M.B.), F-37380 Nouzilly, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Caraty","sequence":"first","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche Physiologie de la Reproduction et des Comportements (Institut National de la Recherche Agronomique, Unit\u00e9 Mixte de Recherche 85; Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 7247 Universit\u00e9 Fran\u00e7ois Rabelais Tours, IFCE) (C.D., K.A., V.R., D.L., J.B.-S., A.C., L.D., M.B.), F-37380 Nouzilly, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Dufourny","sequence":"first","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche Physiologie de la Reproduction et des Comportements (Institut National de la Recherche Agronomique, Unit\u00e9 Mixte de Recherche 85; Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 7247 Universit\u00e9 Fran\u00e7ois Rabelais Tours, IFCE) (C.D., K.A., V.R., D.L., J.B.-S., A.C., L.D., M.B.), F-37380 Nouzilly, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Anderson","sequence":"first","affiliation":[{"name":"Centre for Neuroendocrinology and Department of Anatomy (G.A.), University of Otago School of Medical Sciences, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Beltramo","sequence":"first","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche Physiologie de la Reproduction et des Comportements (Institut National de la Recherche Agronomique, Unit\u00e9 Mixte de Recherche 85; Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 7247 Universit\u00e9 Fran\u00e7ois Rabelais Tours, IFCE) (C.D., K.A., V.R., D.L., J.B.-S., A.C., L.D., M.B.), F-37380 Nouzilly, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2016,2,10]]},"reference":[{"key":"2020071612063630200_B1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.ygcen.2012.02.013","article-title":"Gonadotropin-inhibitory hormone (GnIH): discovery, progress and prospect","volume":"177","author":"Tsutsui","year":"2012","journal-title":"Gen Comp Endocrinol"},{"key":"2020071612063630200_B2","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1111\/j.1365-2826.2010.02031.x","article-title":"The roles of RFamide-related peptide-3 in mammalian reproductive function and behaviour","volume":"22","author":"Kriegsfeld","year":"2010","journal-title":"J Neuroendocrinol"},{"key":"2020071612063630200_B3","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1111\/j.1365-2826.2010.02018.x","article-title":"Discovery and evolutionary history of gonadotrophin-inhibitory hormone and kisspeptin: new key neuropeptides controlling reproduction","volume":"22","author":"Tsutsui","year":"2010","journal-title":"J Neuroendocrinol"},{"key":"2020071612063630200_B4","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/35036326","article-title":"New neuropeptides containing carboxy-terminal RFamide and their receptor in mammals","volume":"2","author":"Hinuma","year":"2000","journal-title":"Nat Cell Biol"},{"key":"2020071612063630200_B5","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1073\/pnas.0511003103","article-title":"Identification and characterization of a gonadotropin-inhibitory system in the brains of mammals","volume":"103","author":"Kriegsfeld","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612063630200_B6","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1210\/en.2007-0848","article-title":"RFamide-related peptide gene is a melatonin-driven photoperiodic gene","volume":"149","author":"Revel","year":"2008","journal-title":"Endocrinology"},{"key":"2020071612063630200_B7","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1210\/en.2011-1622","article-title":"Stimulatory effect of RFRP-3 on the gonadotrophic axis in the male Syrian hamster: the exception proves the rule","volume":"153","author":"Ancel","year":"2012","journal-title":"Endocrinology"},{"key":"2020071612063630200_B8","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1210\/en.2011-1110","article-title":"Identification, expression, and physiological functions of Siberian hamster gonadotropin-inhibitory hormone","volume":"153","author":"Ubuka","year":"2012","journal-title":"Endocrinology"},{"key":"2020071612063630200_B9","doi-asserted-by":"crossref","first-page":"E39","DOI":"10.1152\/ajpendo.00108.2010","article-title":"Characterization of the inhibitory roles of RFRP3, the mammalian ortholog of GnIH, in the control of gonadotropin secretion in the rat: in vivo and in vitro studies","volume":"299","author":"Pineda","year":"2010","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2020071612063630200_B10","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1210\/en.2008-1287","article-title":"Cells expressing RFamide-related peptide-1\/3, the mammalian gonadotropin-inhibitory hormone orthologs, are not hypophysiotropic neuroendocrine neurons in the rat","volume":"150","author":"Rizwan","year":"2009","journal-title":"Endocrinology"},{"key":"2020071612063630200_B11","doi-asserted-by":"crossref","first-page":"5811","DOI":"10.1210\/en.2008-0575","article-title":"Potent action of RFamide-related peptide-3 on pituitary gonadotropes indicative of a hypophysiotropic role in the negative regulation of gonadotropin secretion","volume":"149","author":"Clarke","year":"2008","journal-title":"Endocrinology"},{"key":"2020071612063630200_B12","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1159\/000332822","article-title":"Gonadotropin-inhibitory hormone is a hypothalamic peptide that provides a molecular switch between reproduction and feeding","volume":"95","author":"Clarke","year":"2012","journal-title":"Neuroendocrinology"},{"key":"2020071612063630200_B13","doi-asserted-by":"crossref","first-page":"3368","DOI":"10.1210\/en.2012-1088","article-title":"Gonadotropin-inhibitory hormone (GnIH) secretion into the ovine hypophyseal portal system","volume":"153","author":"Smith","year":"2012","journal-title":"Endocrinology"},{"key":"2020071612063630200_B14","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1111\/j.1365-2826.2012.02283.x","article-title":"RF9 powerfully stimulates gonadotrophin secretion in the ewe: evidence for a seasonal threshold of sensitivity","volume":"24","author":"Caraty","year":"2012","journal-title":"J Neuroendocrinol"},{"key":"2020071612063630200_B15","doi-asserted-by":"crossref","first-page":"4915","DOI":"10.1210\/en.2014-1517","article-title":"RF9 excitation of GnRH neurons is dependent upon Kiss1r in the adult male and female mouse","volume":"155","author":"Liu","year":"2014","journal-title":"Endocrinology"},{"key":"2020071612063630200_B16","doi-asserted-by":"crossref","first-page":"4639","DOI":"10.1210\/en.2015-1635","article-title":"RF9 acts as a KISS1R agonist in vivo and in vitro","volume":"156","author":"Min","year":"2015","journal-title":"Endocrinology"},{"issue":"11","key":"2020071612063630200_B17","doi-asserted-by":"crossref","first-page":"4152","DOI":"10.1210\/en.2015-1532","article-title":"Anxiogenic and stressor effects of the hypothalamic neuropeptide RFRP-3 are overcome by a novel antagonist","volume":"156","author":"Kim","year":"2015","journal-title":"Endocrinology"},{"key":"2020071612063630200_B18","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1095\/biolreprod49.6.1377","article-title":"Seasonal changes in gonadotropin-releasing hormone secretion in the ewe: alteration in response to the negative feedback action of estradiol","volume":"49","author":"Karsch","year":"1993","journal-title":"Biol Reprod"},{"key":"2020071612063630200_B19","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0167-4889(02)00389-0","article-title":"Molecular properties of endogenous RFamide-related peptide-3 and its interaction with receptors","volume":"1593","author":"Yoshida","year":"2003","journal-title":"Biochim Biophys Acta"},{"key":"2020071612063630200_B20","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1111\/j.1365-2826.2008.01784.x","article-title":"RFamide-related peptide and its cognate receptor in the sheep: cDNA cloning, mRNA distribution in the hypothalamus and the effect of photoperiod","volume":"20","author":"Dardente","year":"2008","journal-title":"J Neuroendocrinol"},{"key":"2020071612063630200_B21","doi-asserted-by":"crossref","first-page":"3459","DOI":"10.1021\/jm5019675","article-title":"Rational design of triazololipopeptides analogs of kisspeptin inducing a long-lasting increase of gonadotropins","volume":"58","author":"Beltramo","year":"2015","journal-title":"J Med Chem"},{"key":"2020071612063630200_B22","doi-asserted-by":"crossref","first-page":"3230","DOI":"10.1210\/endo.136.8.7628356","article-title":"Luteinizing hormone (LH)-releasing hormone in third ventricular cerebrospinal fluid of the ewe: correlation with LH pulses and the LH surge","volume":"136","author":"Skinner","year":"1995","journal-title":"Endocrinology"},{"key":"2020071612063630200_B23","doi-asserted-by":"crossref","first-page":"5258","DOI":"10.1210\/en.2007-0554","article-title":"Kisspeptin synchronizes preovulatory surges in cyclical ewes and causes ovulation in seasonally acyclic ewes","volume":"148","author":"Caraty","year":"2007","journal-title":"Endocrinology"},{"key":"2020071612063630200_B24","first-page":"2291","article-title":"[Radio-immunologic determination of the plasma luteinizing hormone in sheep. Determination technic]","volume":"266","author":"Pelletier","year":"1968","journal-title":"C R Acad Sci Hebd Seances Acad Sci D"},{"key":"2020071612063630200_B25","doi-asserted-by":"crossref","first-page":"5549","DOI":"10.1210\/en.2009-0775","article-title":"Effect of RF-amide-related peptide-3 on luteinizing hormone and follicle-stimulating hormone synthesis and secretion in ovine pituitary gonadotropes","volume":"150","author":"Sari","year":"2009","journal-title":"Endocrinology"},{"key":"2020071612063630200_B26","doi-asserted-by":"crossref","first-page":"5770","DOI":"10.1210\/en.2008-0581","article-title":"Variation in kisspeptin and RFamide-related peptide (RFRP) expression and terminal connections to gonadotropin-releasing hormone neurons in the brain: a novel medium for seasonal breeding in the sheep","volume":"149","author":"Smith","year":"2008","journal-title":"Endocrinology"},{"key":"2020071612063630200_B27","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.anireprosci.2015.05.013","article-title":"The role of RFamide-related peptide 3 (RFRP3) in regulation of the neuroendocrine reproductive and growth axes of the boar","volume":"159","author":"Thorson","year":"2015","journal-title":"Anim Reprod Sci"},{"key":"2020071612063630200_B28","first-page":"566","article-title":"Effects of RFamide-related peptide-3(RFRP-3) on secretion of LH in ovariectomized prepubertal gilts","volume":"88E","author":"Heidorn","year":"2010","journal-title":"J Anim Sci"},{"key":"2020071612063630200_B29","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1095\/biolreprod.113.112185","article-title":"Hypothalamic distribution, adenohypophyseal receptor expression, and ligand functionality of RFamide-related peptide 3 in the mare during the breeding and nonbreeding seasons","volume":"90","author":"Thorson","year":"2014","journal-title":"Biol Reprod"},{"key":"2020071612063630200_B30","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1073\/pnas.0502090103","article-title":"RF9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid-induced tolerance associated with hyperalgesia","volume":"103","author":"Simonin","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612063630200_B31","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.neuropharm.2013.07.012","article-title":"Endogenous mammalian RF-amide peptides, including PrRP, kisspeptin and 26RFa, modulate nociception and morphine analgesia via NPFF receptors","volume":"75C","author":"Elhabazi","year":"2013","journal-title":"Neuropharmacology"},{"key":"2020071612063630200_B32","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1210\/en.2011-1260","article-title":"Kisspeptin signaling is indispensable for neurokinin B, but not glutamate, stimulation of gonadotropin secretion in mice","volume":"153","author":"Garcia-Galliano","year":"2011","journal-title":"Endocrinology"},{"key":"2020071612063630200_B33","doi-asserted-by":"crossref","first-page":"11324","DOI":"10.1073\/pnas.0901176106","article-title":"Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats","volume":"106","author":"Kirby","year":"2009","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/157\/4\/1566\/8995949\/endo1566.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/157\/4\/1566\/8995949\/endo1566.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T08:38:55Z","timestamp":1718354335000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/157\/4\/1566\/2422608"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,10]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,4,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2015-1854","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,10]]}}}