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Gonadotropin-releasing hormone (GnRH) is the initial trigger for HPGA activation and plays an important role in puberty onset. N-methyl-D-aspartate (NMDA) can promote pulsatile GnRH secretion and accelerates puberty onset. However, the mechanism of N-methyl-D-aspartate receptors (NMDARs) in PP pathogenesis remains obscure. We found that serum GnRH, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogen (E2) levels, hypothalamic NMDAR1, and GnRH mRNA expression peaked at the vaginal opening (VO) day. Next, the hypothalamic NMDAR1 mRNA and protein levels in rats treated with danazol, a chemical commonly effecting on the reproductive system, were significantly increased at the VO day (postnatal day 24) compared to controls, accompanied by enhanced serum GnRH, LH, FSH, and E2 levels. Further, microRNA-664-2 (miR-664-2) was selected after bioinformatics analysis and approved in primary hypothalamic neurons, which binds to the 3\u2032-untranslated regions of NMDAR1. Consistently, the miR-664-2 expression in hypothalamus of the Danazol group was decreased compared to Vehicle. Our results suggested that attenuated miR-664-2 might participate in PP pathogenesis through enhancing the NMDAR1 signaling.<\/jats:p>","DOI":"10.1093\/biolre\/ioz044","type":"journal-article","created":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T23:11:12Z","timestamp":1553728272000},"page":"1536-1548","source":"Crossref","is-referenced-by-count":11,"title":["MiR-664-2 impacts pubertal development in a precocious-puberty rat model through targeting the NMDA receptor-1\u2020"],"prefix":"10.1093","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9688-3359","authenticated-orcid":false,"given":"Minda","family":"Ju","sequence":"first","affiliation":[{"name":"Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Institute of Acupuncture and Moxibustion Research, Academy of Integrative Medicine, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[{"name":"Shanghai Dunlu Biomedical Technology Co., Ltd, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Institute of Acupuncture and Moxibustion Research, Academy of Integrative Medicine, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhejun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Institute of Acupuncture and Moxibustion Research, Academy of Integrative Medicine, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Institute of Acupuncture and Moxibustion Research, Academy of Integrative Medicine, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Institute of Acupuncture and Moxibustion Research, Academy of Integrative Medicine, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanzhuang","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Institute of Acupuncture and Moxibustion Research, Academy of Integrative Medicine, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,3,27]]},"reference":[{"issue":"3","key":"2020071700352598000_bib1","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.adolescence.2008.07.005","article-title":"Pubertal timing and its link to behavioral and emotional problems among \u2018at-risk\u2019 African American adolescent girls","volume":"32","author":"Carter","year":"2009","journal-title":"J 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