{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:59:56Z","timestamp":1792645196274,"version":"4.5.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Polycystic ovarian syndrome (PCOS) is a heterogeneous endocrine disorder in reproductive-age women, characterized by the accretion of small cystic follicles in the ovary associated with chronic anovulation and overproduction of androgens. Ovarian function in all mammals is controlled by gonadotropin-releasing hormone (GnRH) neurons, which are the central regulator of the hypothalamic-pituitary-gonadal (HPG) axis. However, the impact on the neurotransmitter system regulating GnRH neuronal function in the letrozole-induced PCOS mouse model remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we compared the response of various neurotransmitters and neurosteroids regulating GnRH neuronal activities between letrozole-induced PCOS and normal mice <jats:italic>via<\/jats:italic> electrophysiological techniques.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Response to neurotransmitter systems like GABAergic, glutamatergic and kisspeptinergic were suppressed in letrozole-fed compared to normal mice. In addition, neurosteroids tetrahydrodeoxycorticosterone (THDOC) and 4,5,6,7-tetrahydroisoxazolo[5,4-c] pyridine-3-ol (THIP) mediated response on GnRH neurons were significantly smaller on letrozole-fed mice compared to normal mice. Furthermore, we also found that letrozole-fed mice showed irregularity in the estrous cycle, increased body weight, and anovulation in female mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest that PCOS is an endocrine disorder that may directly affect the neurotransmitter system regulating GnRH neuronal activity at the hypothalamic level and impact reproductive physiology.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.1059255","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T12:30:12Z","timestamp":1673267412000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Suppression of neurotransmission on gonadotropin-releasing hormone neurons in letrozole-induced polycystic ovary syndrome: A mouse model"],"prefix":"10.3389","volume":"13","author":[{"given":"Pravin","family":"Bhattarai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh","family":"Rijal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janardhan P.","family":"Bhattarai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Hyu","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Kyu","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-16-3-322","article-title":"Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion","volume":"16","author":"Ehrman","year":"1995","journal-title":"Endocr Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.2004.tb05838.x","article-title":"Polycystic ovary syndrome","volume":"180","author":"Norman","year":"2004","journal-title":"Med J Aust"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.111.097808","article-title":"Rodent models for human polycystic ovary syndrome","volume":"86","author":"Walters","year":"2012","journal-title":"Biol Reprod"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1055\/s-0034-1371092","article-title":"Childhood obesity and its impact on the development of adolescent PCOS","volume":"32","author":"Anderson","year":"2014","journal-title":"Semin Reprod Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"599","DOI":"10.3109\/00016349209006227","article-title":"Oden a polycystic ovary syndrome and risk for myocardial infarction: evaluated from a risk factor model based on a prospective population study of women","volume":"71","author":"Dahlgren","year":"1992","journal-title":"Acta Obstet. 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