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Numerous studies have shown the effects of melatonin on the release of gonadotropins and their actions at one or several levels of the hypothalamic\u2013pituitary\u2013gonadal axis. However, direct melatonin action on gonadotropin-releasing hormone (GnRH) neurons and its mechanism of action remain unclear. Here, plasma melatonin levels were measured and the effect of melatonin on GnRH neurons was assessed using brain slice patch clamp techniques. The plasma melatonin levels in prepubertal mice were higher than those in the adults. Melatonin itself did not change the firing activity of GnRH neurons. Interestingly, the kainate receptor-mediated responses but not the \u03b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartic acid (NMDA)-induced responses were suppressed by melatonin in both the voltage clamp and current clamp modes. The inhibitory effects of the kainate-induced response by melatonin tended to increase with higher melatonin concentrations and persisted in the presence of tetrodotoxin, a voltage-sensitive Na+ channel blocker, or luzindole, a non-selective melatonin receptor antagonist. However, the response was completely abolished by pretreatment with pertussis toxin. These results suggest that melatonin can regulate GnRH neuronal activities in prepubertal mice by partially suppressing the excitatory signaling mediated by kainate receptors through pertussis toxin-sensitive G-protein-coupled receptors.<\/jats:p>","DOI":"10.3390\/ijms21175991","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T09:35:31Z","timestamp":1597916131000},"page":"5991","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Melatonin Suppresses the Kainate Receptor-Mediated Excitation on Gonadotropin-Releasing Hormone Neurons in Female and Male Prepubertal Mice"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1924-4457","authenticated-orcid":false,"given":"Santosh","family":"Rijal","sequence":"first","affiliation":[{"name":"Department of Oral Physiology, School of Dentistry &amp; Institute of Oral Bioscience, Jeonbuk National University, Jeonju 54896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Hyu","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Jeonbuk National University Medical School, Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute and Institute for Medical Sciences, Jeonbuk National University Hospital, Jeonju 54907, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9782-5399","authenticated-orcid":false,"given":"Seon-Ah","family":"Park","sequence":"additional","affiliation":[{"name":"Non-Clinical Evaluation Center, Biomedical Research Institute, 20 Geonji-ro, Deokjin-gu, Jeonju-si, Jeollabuk-do 54907, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon Hui","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Oral Physiology, School of Dentistry &amp; Institute of Oral Bioscience, Jeonbuk National University, Jeonju 54896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istv\u00e1n M.","family":"\u00c1brah\u00e1m","sequence":"additional","affiliation":[{"name":"PTE-NAP Molecular Neuroendocrinology Research Group, Institute of Physiology, Medical School, Centre for Neuroscience, Szent\u00e1gothai Research Center, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Kyu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Oral Physiology, School of Dentistry &amp; Institute of Oral Bioscience, Jeonbuk National University, Jeonju 54896, Korea"},{"name":"PTE-NAP Molecular Neuroendocrinology Research Group, Institute of Physiology, Medical School, Centre for Neuroscience, Szent\u00e1gothai Research Center, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/nrendo.2016.70","article-title":"Control of puberty onset and fertility by gonadotropin-releasing hormone neurons","volume":"12","author":"Herbison","year":"2016","journal-title":"Nat. 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