{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:56:03Z","timestamp":1790556963708,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/005913\/1"],"award-info":[{"award-number":["BB\/005913\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Pulsatile gonadotropin\u2010releasing hormone (GnRH) and luteinizing hormone (LH) secretion are essential for reproductive function and are thought to be governed by arcuate nucleus kisspeptin Kiss1\n                    <jats:sup>ARH<\/jats:sup>\n                    neurons via neurokinin B (NKB) signaling through TacR3. However, discrepancies between ex vivo and in vivo pharmacology limit mechanistic understanding of how TacR3 activation regulates pulsatile hormone release. We developed and synthesized a photoswitchable TacR3 agonist (\n                    <jats:italic>azo<\/jats:italic>\n                    \u2010senktide) and characterized its photochemical and pharmacological properties using UV\u2013Vis spectroscopy, TacR3\u2010expressing HEK293T cells, electrophysiology in mouse hypothalamic slices, and in vivo optofluidic delivery combined with light stimulation to assess LH secretion in freely moving mice.\n                    <jats:italic>Azo<\/jats:italic>\n                    \u2010senktide reversibly photoisomerized between inactive (trans) and more potent (cis) conformations. In cells, light activation enhanced TacR3\u2010mediated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling. In brain slices, photostimulation depolarized and increased firing of Kiss1\n                    <jats:sup>ARH<\/jats:sup>\n                    neurons through a mechanism consistent with the established TacR3\u2013TRPC5 signaling pathway. In vivo, optical activation of\n                    <jats:italic>azo<\/jats:italic>\n                    \u2010senktide in the arcuate nucleus elicited a time\u2010locked LH pulse at an intermediate dose, whereas lower or higher doses were ineffective, indicating a nonlinear, dose\u2010dependent response. These findings demonstrate that temporally gated TacR3 activation via photoswitchable\n                    <jats:italic>azo<\/jats:italic>\n                    \u2010senktide evokes an increase in LH, revealing that neurokinin B signaling in the Kiss1\n                    <jats:sup>ARH<\/jats:sup>\n                    network depends on activation dynamics, reconciles inconsistencies, and establishes photopharmacology as a powerful approach for probing neuroendocrine timing mechanisms.\n                  <\/jats:p>","DOI":"10.1111\/jne.70255","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:56:13Z","timestamp":1788915373000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optical control of the hypothalamic arcuate nucleus kisspeptin neuronal network with a photoswitchable peptide that drives luteinizing hormone release in female mice"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4988-8587","authenticated-orcid":false,"given":"Jian","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Chemical Physiology and Biochemistry Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3472-6990","authenticated-orcid":false,"given":"Yanyan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Women and Children's Health, School of Life Course and Population Sciences King's College London, Guy's Campus  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9435-072X","authenticated-orcid":false,"given":"Emily","family":"Bartram","sequence":"additional","affiliation":[{"name":"Department of Women and Children's Health, School of Life Course and Population Sciences King's College London, Guy's Campus  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1700-2646","authenticated-orcid":false,"given":"Janelle M.","family":"Tobias","sequence":"additional","affiliation":[{"name":"Department of Chemical Physiology and Biochemistry Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8340-8842","authenticated-orcid":false,"given":"Antonio","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Oregon Health &amp; Science University Vollum Institute  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9974-1340","authenticated-orcid":false,"given":"Xiao Feng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Women and Children's Health, School of Life Course and Population Sciences King's College London, Guy's Campus  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria S.","family":"Halls","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Core Facility Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6705-2540","authenticated-orcid":false,"given":"James A.","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Chemical Physiology and Biochemistry Oregon Health &amp; Science University  Portland Oregon USA"},{"name":"Oregon Health &amp; Science University Vollum Institute  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8633-2510","authenticated-orcid":false,"given":"Martin J.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Chemical Physiology and Biochemistry Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2548-4182","authenticated-orcid":false,"given":"Kevin T.","family":"O'Byrne","sequence":"additional","affiliation":[{"name":"Department of Women and Children's Health, School of Life Course and Population Sciences King's College London, Guy's Campus  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1569-09.2009"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0022"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1512243112"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.16246"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0622-21.2021"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.96691"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1415226112"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1713897114"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00517.2010"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1641"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1574"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.5b00129"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c01415"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9CC03346G"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c18379"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.06.037"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.35656"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-29-09529.2003"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.03.004"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4816-09.2010"},{"key":"e_1_2_10_23_1","volume-title":"The Mouse Brain in Stereotaxic Coordinates","author":"Franklin KBJ","year":"2008"},{"key":"e_1_2_10_24_1","article-title":"Frequent tail\u2010tip blood sampling in mice for the assessment of pulsatile luteinizing hormone secretion","volume":"137","author":"McCosh RB","year":"2018","journal-title":"J Vis Exp"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1351"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-1502"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(94)00681-V"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coemr.2020.09.007"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-12-14"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1208592"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2018.05.004"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2018-00653"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0828-19.2019"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.09.010"}],"container-title":["Journal of Neuroendocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jne.70255","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jne.70255","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jne.70255","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:05:42Z","timestamp":1790553942000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jne.70255"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":33,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/jne.70255"],"URL":"https:\/\/doi.org\/10.1111\/jne.70255","archive":["Portico"],"relation":{},"ISSN":["0953-8194","1365-2826"],"issn-type":[{"value":"0953-8194","type":"print"},{"value":"1365-2826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-01-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70255"}}