{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T07:20:35Z","timestamp":1778916035866,"version":"3.51.4"},"reference-count":84,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Australian National Health and Medical Research Council","award":["APP1158540"],"award-info":[{"award-number":["APP1158540"]}]},{"name":"Australian National Health and Medical Research Council","award":["APP1117538"],"award-info":[{"award-number":["APP1117538"]}]},{"DOI":"10.13039\/501100001114","name":"Endocrine Society of Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001114","id-type":"DOI","asserted-by":"publisher"}]},{"name":"School of Women\u2019s and Children\u2019s Health"},{"name":"University of New South Wales Sydney"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Polycystic ovary syndrome (PCOS) is a prevalent endocrine condition characterized by a range of endocrine, reproductive, and metabolic abnormalities. At present, management of women with PCOS is suboptimal as treatment is only symptomatic. Clinical and experimental advances in our understanding of PCOS etiology support a pivotal role for androgen neuroendocrine actions in PCOS pathogenesis. Hyperandrogenism is a key PCOS trait and androgen actions play a role in regulating the kisspeptin-\/neurokinin B-\/dynorphin (KNDy) system. This study aimed to investigate if targeted antagonism of neurokinin B signaling through the neurokinin 3 receptor (NK3R) would reverse PCOS traits in a dihydrotestosterone (DHT)-induced mouse model of PCOS. After 3 months, DHT exposure induced key reproductive PCOS traits of cycle irregularity and ovulatory dysfunction, and PCOS-like metabolic traits including increased body weight; white and brown fat pad weights; fasting serum triglyceride and glucose levels, and blood glucose incremental area under the curve. Treatment with a NK3R antagonist (MLE4901) did not impact the observed reproductive defects. In contrast, following NK3R antagonist treatment, PCOS-like females displayed decreased total body weight, adiposity, and adipocyte hypertrophy, but increased respiratory exchange ratio, suggesting NK3R antagonism altered the metabolic status of the PCOS-like females. NK3R antagonism did not improve circulating serum triglyceride or fasted glucose levels. Collectively, these findings demonstrate that NK3R antagonism may be beneficial in the treatment of adverse metabolic features associated with PCOS and support neuroendocrine targeting in the development of novel therapeutic strategies for PCOS.<\/jats:p>","DOI":"10.1210\/endocr\/bqab020","type":"journal-article","created":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T15:34:47Z","timestamp":1612193687000},"source":"Crossref","is-referenced-by-count":23,"title":["Neurokinin 3 Receptor Antagonism Ameliorates Key Metabolic Features in a Hyperandrogenic PCOS Mouse Model"],"prefix":"10.1210","volume":"162","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7592-5855","authenticated-orcid":false,"given":"Irene E","family":"Sucquart","sequence":"first","affiliation":[{"name":"Fertility and Research Centre, School of Women\u2019s & Children\u2019s Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruchi","family":"Nagarkar","sequence":"additional","affiliation":[{"name":"Fertility and Research Centre, School of Women\u2019s & Children\u2019s Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa C","family":"Edwards","sequence":"additional","affiliation":[{"name":"Fertility and Research Centre, School of Women\u2019s & Children\u2019s Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0880-6661","authenticated-orcid":false,"given":"Valentina","family":"Rodriguez Paris","sequence":"additional","affiliation":[{"name":"Fertility and Research Centre, School of Women\u2019s & Children\u2019s Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9004-6920","authenticated-orcid":false,"given":"Ali","family":"Aflatounian","sequence":"additional","affiliation":[{"name":"Fertility and Research Centre, School of Women\u2019s & Children\u2019s Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9471-501X","authenticated-orcid":false,"given":"Michael J","family":"Bertoldo","sequence":"additional","affiliation":[{"name":"Fertility and Research Centre, School of Women\u2019s & Children\u2019s Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0309-532X","authenticated-orcid":false,"given":"Rebecca E","family":"Campbell","sequence":"additional","affiliation":[{"name":"Centre of Neuroendocrinology and Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1611-7142","authenticated-orcid":false,"given":"Robert B","family":"Gilchrist","sequence":"additional","affiliation":[{"name":"Fertility and Research Centre, School of Women\u2019s & Children\u2019s Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4551-2697","authenticated-orcid":false,"given":"Denovan P","family":"Begg","sequence":"additional","affiliation":[{"name":"Department of Behavioural Neuroscience, School of Psychology, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4200-7476","authenticated-orcid":false,"given":"David J","family":"Handelsman","sequence":"additional","affiliation":[{"name":"Andrology Laboratory, ANZAC Research Institute, University of Sydney, Concord Hospital, NSW 2139, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8443-7212","authenticated-orcid":false,"given":"Vasantha","family":"Padmanabhan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7495-518X","authenticated-orcid":false,"given":"Richard A","family":"Anderson","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1504-9734","authenticated-orcid":false,"given":"Kirsty A","family":"Walters","sequence":"additional","affiliation":[{"name":"Fertility and Research Centre, School of Women\u2019s & Children\u2019s Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"issue":"2","key":"2021121713512810000_CIT0001","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1093\/humrep\/dep399","article-title":"The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria","volume":"25","author":"March","year":"2010","journal-title":"Hum Reprod."},{"issue":"12","key":"2021121713512810000_CIT0002","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1093\/humrep\/dew218","article-title":"The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis","volume":"31","author":"Bozdag","year":"2016","journal-title":"Hum 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