https://m2.mtmt.hu/ eng 2026-10-25 20:50 JournalArticle 35663177 VALIDATED true Funding Agency and Grant Number: National Laboratory of Translational Neuroscience; Recovery and Resilience Facility of the European Union; National Research, Development and Innovation Office [K138137, PD134837]; Hungarian Research Network; New National Excellence Programme of Hungary; Award of the National Academy of Scientist Education program; [RRF-2.3.1-21-2022-00011]; [SA-104/2021] Funding text: This work was supported by grants to Project Number RRF-2.3.1-21-2022-00011, titled National Laboratory of Translational Neuroscience implemented with the support provided by the Recovery and Resilience Facility of the European Union within the framework of Programme Szechenyi Plan Plus, the National Research, Development and Innovation Office (K138137 to E.H. and PD134837 to K.S.) , and the Hungarian Research Network (SA-104/2021) . S.S.-T. and B.Go. are awardees of the New National Excellence Programme of Hungary. The work of S.S.-T. received support by the award of the National Academy of Scientist Education program. 0 false 2026-10-25T19:14:44.752+0000 2026-07-20T13:13:53.177+0000 2025-01-06T09:40:14.900+0000 true 10065463 Turek Márta /api/admin/10065463 Admin true 2026-08-03T13:03:31.966+0000 2025-10-15T11:26:08.533+0000 true 10022176 Laczik Cecilia /api/admin/10022176 Admin true 10022176 Admin 10025544 /api/admin/10025544 Lévayné Deseő Katalin true 10025544 true 2026-05-20T07:50:03.540+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Szentkirályi-Tóth, Soma Estrogen-regulated lateral septal kisspeptin neurons abundantly project to GnRH neurons and the hypothalamic supramammillary nucleus. true true /api/journal/2707 REVIEWED true false 2707 false 2707 true 0270-6474 1529-2401 Journal FOREIGN 45 8 e1307242024 e1307242024 20 2025 While hypothalamic kisspeptin (KP) neurons play well-established roles in the estrogen-dependent regulation of reproduction, little is known about extrahypothalamic KP-producing (KPLS) neurons of the lateral septum. As established previously, Kiss1 expression in this region is low and regulated by estrogen receptor- and GABAB receptor-dependent mechanisms. Our present experiments on Kiss1-Cre/ZsGreen knock-in mice revealed that transgene expression in the LS begins at P33-36 in females and P40-45 in males and is stimulated by estrogen receptor signaling. Fluorescent cell numbers continue to increase in adulthood and, regardless of age, remain higher in females. Viral tracing uncovered that the bulk of KPLS fibers joins the medial forebrain bundle and terminates in the hypothalamic supramammillary nucleus. Smaller subsets of the axons innervate the medial amygdala or project to other limbic structures. One-quarter of gonadotropin-releasing hormone-immunoreactive perikarya in the preoptic area and their dendrites receive appositions from KPLS axons. Ovariectomized adult Kiss1-Cre/ZsGreen mice treated for 4 days with 17β-estradiol or vehicle were used for RNA-Seq studies of laser-microdissected KPLS neurons. The transcriptome included markers of GABAergic and neuropeptidergic (Penk, Cartpt, Vgf) cotransmission and 571 estrogen-regulated transcripts. Estrogen treatment upregulated the acetylcholine receptor transcript Chrm2 and, in slice electrophysiology experiments, caused enhanced muscarinic inhibition of KPLS neurons. Finally, we provided immunohistochemical evidence for homologous neurons in the post mortem human brain, suggesting that KPLS neurons may contribute to evolutionarily conserved regulatory mechanisms. Future studies will need to investigate the putative roles of KPLS neurons in the estrogen-dependent control of gonadotropin-releasing hormone neurons and/or various hypothalamic/limbic functions.Significance Statement Gonadotropin-releasing hormone (GnRH) neurons of the hypothalamus stimulate pituitary gonadotropin secretion to promote gonadal functions. Sex steroids of the gonads serve as feedback signals to control the hypothalamic output of GnRH. According to current consensus, steroid feedback is mainly sensed and communicated to the GnRH neuronal system by sex steroid-sensitive hypothalamic cell groups through the neuropeptide kisspeptin.Anatomical, developmental, spatial transcriptomic and electrophysiological characterization of an extrahypothalamic kisspeptin system in this study unveils the previously unexplored contribution of lateral septal kisspeptin cells to the sex-steroid dependent afferent control of GnRH neurons. Identification of analogous kisspeptin neurons in the post mortem human brain suggests that this estrogen dependent system may play an evolutionarily conserved role in the central regulation of reproduction. 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<img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="10098656"><a href="/gui2/?type=authors&mode=browse&sel=10098656" target="_blank">Szentkirályi-Tóth Soma (<span class="authorship-author-name">Szentkirályi-Tóth Soma</span> <span class="authorAux-mtmt"> Reproduktív Neurobiológia, Neurobiológia</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Institute of Experimental Medicine">HUN-REN IEM</span>/Laboratory of Reproductive Neurobiology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10062868"><a href="/gui2/?type=authors&mode=browse&sel=10062868" target="_blank">Göcz Balázs<sup>*</sup> (<span class="authorship-author-name">Göcz Balázs Gergő</span> <span class="authorAux-mtmt"> Reproduktív neurobiológia</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Institute of Experimental Medicine">HUN-REN IEM</span>/Laboratory of Reproductive Neurobiology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10028898"><a href="/gui2/?type=authors&mode=browse&sel=10028898" target="_blank">Takács Szabolcs (<span class="authorship-author-name">Takács Szabolcs Ferenc</span> <span class="authorAux-mtmt"> neuroendokrinológia</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Institute of Experimental Medicine">HUN-REN IEM</span>/Laboratory of Reproductive Neurobiology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10014210"><a href="/gui2/?type=authors&mode=browse&sel=10014210" target="_blank">Sárvári Miklós (<span class="authorship-author-name">Sárvári Miklós</span> <span class="authorAux-mtmt"> Endokrin neurobiológia</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Institute of Experimental Medicine">HUN-REN IEM</span>/Laboratory of Reproductive Neurobiology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10011497"><a href="/gui2/?type=authors&mode=browse&sel=10011497" target="_blank">Farkas Imre (<span class="authorship-author-name">Farkas Imre</span> <span class="authorAux-mtmt"> Neurobiológia</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Institute of Experimental Medicine">HUN-REN IEM</span>/Laboratory of Reproductive Neurobiology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10020450"><a href="/gui2/?type=authors&mode=browse&sel=10020450" target="_blank">Skrapits Katalin (<span class="authorship-author-name">Skrapits Katalin</span> <span class="authorAux-mtmt"> neuroendokrinológia/reproduktív neurobiológia</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Institute of Experimental Medicine">HUN-REN IEM</span>/Laboratory of Reproductive Neurobiology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10060241"><a href="/gui2/?type=authors&mode=browse&sel=10060241" target="_blank">Rumpler Éva (<span class="authorship-author-name">Rumpler Éva</span> <span class="authorAux-mtmt"> Biológia</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Institute of Experimental Medicine">HUN-REN IEM</span>/Laboratory of Reproductive Neurobiology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10028436"><a href="/gui2/?type=authors&mode=browse&sel=10028436" target="_blank">Póliska Szilárd (<span class="authorship-author-name">Póliska Szilárd</span> <span class="authorAux-mtmt"> Elméleti orvostudományok</span>) </a> </span> <span class="author-affil"><span title="University of Debrecen">UD</span>/<span title="Faculty of Medicine">Faculty of Medicine</span>/Department of Biochemistry and Molecular Biology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10023602"><a href="/gui2/?type=authors&mode=browse&sel=10023602" target="_blank">Rácz Gergely ✉ (<span class="authorship-author-name">Rácz Gergely</span> <span class="authorAux-mtmt"> Patológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Patológiai és Kísérleti Rákkutató Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10000495"><a href="/gui2/?type=authors&mode=browse&sel=10000495" target="_blank">Matolcsy András (<span class="authorship-author-name">Matolcsy András</span> <span class="authorAux-mtmt"> Pathológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Patológiai és Kísérleti Rákkutató Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Ternier Gaëtan </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Fernandois Daniela </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Giacobini Paolo </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Prévot Vincent </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Colledge William H </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="136"><a href="/gui2/?type=authors&mode=browse&sel=136" target="_blank">Wittmann Gábor (<span class="authorship-author-name">Wittmann Gábor</span> <span class="authorAux-mtmt"> Endokrin neurobiológia</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Institute of Experimental Medicine">HUN-REN IEM</span>/Integratív Neuroendokrinológiai Kutatócsoport</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="205"><a href="/gui2/?type=authors&mode=browse&sel=205" target="_blank">Kádár Andrea (<span class="authorship-author-name">Kádár Andrea</span> <span class="authorAux-mtmt"> Integratív neuroendokrinológia</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Institute of Experimental Medicine">HUN-REN IEM</span>/Integratív Neuroendokrinológiai Kutatócsoport</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10023404"><a href="/gui2/?type=authors&mode=browse&sel=10023404" target="_blank">Mohácsik Petra (<span class="authorship-author-name">Mohácsik Petra</span> <span class="authorAux-mtmt"> Neuroendokrinológia</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Institute of Experimental Medicine">HUN-REN IEM</span>/Laboratory of Molecular Cell Metabolism</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10011473"><a href="/gui2/?type=authors&mode=browse&sel=10011473" target="_blank">Gereben Balázs (<span class="authorship-author-name">Gereben Balázs</span> <span class="authorAux-mtmt"> Pajzsmirigy endokrinológia</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Institute of Experimental Medicine">HUN-REN IEM</span>/Laboratory of Molecular Cell Metabolism</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10012354"><a href="/gui2/?type=authors&mode=browse&sel=10012354" target="_blank">Fekete Csaba (<span class="authorship-author-name">Fekete Csaba</span> <span class="authorAux-mtmt"> Neuroendokrinológia</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Institute of Experimental Medicine">HUN-REN IEM</span>/Integratív Neuroendokrinológiai Kutatócsoport</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10011472"><a href="/gui2/?type=authors&mode=browse&sel=10011472" target="_blank">Hrabovszky Erik ✉ (<span class="authorship-author-name">Hrabovszky Erik</span> <span class="authorAux-mtmt"> Reproduktív endokrinológia</span>) </a> </span> <span class="author-affil"><span title="HUN-REN Institute of Experimental Medicine">HUN-REN IEM</span>/Laboratory of Reproductive Neurobiology</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;35663177" target="_blank">Estrogen-regulated lateral septal kisspeptin neurons abundantly project to GnRH neurons and the hypothalamic supramammillary nucleus.</a></div> <div> <span class="journal-title">JOURNAL OF NEUROSCIENCE</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/0270-6474">0270-6474</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1529-2401">1529-2401</a>)</span>: <span class="journal-volume">45</span> <span class="journal-issue">8</span> <span class="page"> Paper e1307242024. 20 p. </span> <span class="year">(2025)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Language: English | </span> <span class="identifiers"> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="10.1523/JNEUROSCI.1307-24.2024" target="_blank" href="https://doi.org/10.1523/JNEUROSCI.1307-24.2024"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="001434287800008" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/001434287800008"> WoS </a> </span> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:black" title="243182" target="_blank" href="https://real.mtak.hu/243182"> REAL </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85219524677" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85219524677"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="39746822" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=39746822&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Journal subject: Scopus - Neuroscience (miscellaneous)&nbsp;&nbsp;&nbsp;Rank:&nbsp;Q1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="" class="citingPub-count">Citing papers: 10</span> | Independent citation: 10 | Self citation: 0 | Unknown citation: 0 | Number of citations in WoS: 10 | Number of citations in Scopus:&nbsp;10 | WoS/Scopus assigned:&nbsp;10 | Number of citations with DOI:&nbsp;10 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;35663177&sort=publishedYear,desc&sort=title"> Number of cited publications: 15 </a> </div> <div class="mtid"><span class="long-pub-mtid">Publication: 35663177</span> | <span class="status-data status-VALIDATED"> Validated </span> Core Citing | <span class="type-subtype">Journal Article ( Article ) </span> | <span class="pub-category">Scientific</span> | <span class="publication-sourceOfData">kézi felvitel</span> </div> <div class="funder"> (Recovery and Resilience Facility of the European Union within the framework of Programme Széchenyi Plan Plus grant number RRF-2.3.1-21-2022-00011), National Laboratory of Translational Neuroscience (TINL)(RRF-2.3.1-21-2022-00011), National Science Foundation of Hungary(K138137), National Science Foundation of Hungary(PD134837) </div> <div class="lastModified">Last Modified: 2026.07.20. 15:13 László Szendrei (DE/BTK admin5) </div> <div class="lockedBy">Centrally managed 2026.05.20. 09:50 Katalin Lévayné Deseő (MTMT Központi admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Comments</u>: Funding Agency and Grant Number: National Laboratory of Translational Neuroscience; Recovery and Resilience Facility of the European Union; National Research, Development and Innovation Office [K138137, PD134837]; Hungarian Research Network; New National Excellence Programme of Hungary; Award of the National Academy of Scientist Education program; [RRF-2.3.1-21-2022-00011]; [SA-104/2021] ...</pre> </div></div>