{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:40:10Z","timestamp":1790613610049,"version":"4.1.0"},"reference-count":94,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T00:00:00Z","timestamp":1628812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"National Cancer Institute Cancer Center","award":["# NIH 5 P30 CA06516"],"award-info":[{"award-number":["# NIH 5 P30 CA06516"]}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32HL007609-31"],"award-info":[{"award-number":["T32HL007609-31"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F32HD097963"],"award-info":[{"award-number":["F32HD097963"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R24HD102061"],"award-info":[{"award-number":["R24HD102061"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Recent evidence suggests that vasomotor symptoms (VMS) or hot flashes in the postmenopausal reproductive state and polycystic ovary syndrome (PCOS) in the premenopausal reproductive state emanate from the hyperactivity of Kiss1 neurons in the hypothalamic infundibular\/arcuate nucleus (KNDy neurons).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We demonstrate in 2 murine models simulating menopause and PCOS that a peripherally restricted kappa receptor agonist (PRKA) inhibits hyperactive KNDy neurons (accessible from outside the blood\u2013brain barrier) and impedes their downstream effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Case\/control.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Academic medical center.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>Mice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Interventions<\/jats:title>\n                  <jats:p>Administration of peripherally restricted kappa receptor agonists and frequent blood sampling to determine hormone release and body temperature.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>LH pulse parameters and body temperature.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>First, chronic administration of a PRKA to bilaterally ovariectomized mice with experimentally induced hyperactivity of KNDy neurons reduces the animals\u2019 elevated body temperature, mean plasma LH level, and mean peak LH per pulse. Second, chronic administration of a PRKA to a murine model of PCOS, having elevated plasma testosterone levels and irregular ovarian cycles, suppresses circulating levels of LH and testosterone and restores normal ovarian cyclicity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The inhibition of kisspeptin neuronal activity by activation of kappa receptors shows promise as a novel therapeutic approach to treat both VMS and PCOS in humans.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgab602","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T11:41:22Z","timestamp":1628854882000},"page":"e328-e347","source":"Crossref","is-referenced-by-count":34,"title":["Inhibiting Kiss1 Neurons With Kappa Opioid Receptor Agonists to Treat Polycystic Ovary Syndrome and Vasomotor Symptoms"],"prefix":"10.1210","volume":"107","author":[{"given":"Elizabeth A","family":"McCarthy","sequence":"first","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Dischino","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Maguire","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Leon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajae","family":"Talbi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio D","family":"Schteingart","sequence":"additional","affiliation":[{"name":"Peptide Logic LLC, San Diego, CA 92121, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre J M","family":"Rivi\u00e8re","sequence":"additional","affiliation":[{"name":"Peptide Logic LLC, San Diego, CA 92121, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan D","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A","family":"Steiner","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, University of Washington, Seattle, WA 98195, USA"},{"name":"Department of Physiology & Biophysics, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5799-219X","authenticated-orcid":false,"given":"Victor M","family":"Navarro","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Harvard Program in Neuroscience, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,8,13]]},"reference":[{"issue":"8","key":"2021121823121745900_CIT0001","doi-asserted-by":"crossref","first-page":"3479","DOI":"10.1210\/en.2010-0022","article-title":"Minireview: kisspeptin\/neurokinin B\/dynorphin (KNDy) cells of the arcuate nucleus: a central node in the control of gonadotropin-releasing hormone 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