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DOI10.1073/pnas.2009156118
Direct evidence that KNDy neurons maintain gonadotropin pulses and folliculogenesis as the GnRH pulse generator
Nagae M.; Uenoyama Y.; Okamoto S.; Tsuchida H.; Ikegami K.; Goto T.; Majarune S.; Nakamura S.; Sanbo M.; Hirabayashi M.; Kobayashi K.; Inoue N.; Tsukamura H.
发表日期2021
ISSN00278424
卷号118期号:5
英文摘要The gonadotropin-releasing hormone (GnRH) pulse is fundamental for mammalian reproduction: GnRH pulse regimens are needed as therapies for infertile women as continuous GnRH treatment paradoxically inhibits gonadotropin release. Circumstantial evidence suggests that the hypothalamic arcuate KNDy neurons expressing kisspeptin (encoded by Kiss1), neurokinin B (encoded by Tac3), and dynorphin A serve as a GnRH pulse generator; however, no direct evidence is currently available. Here, we show that rescuing >20% KNDy neurons by transfecting Kiss1 inside arcuate Tac3 neurons, but not outside of these neurons, recovered folliculogenesis and luteinizing hormone (LH) pulses, an indicator of GnRH pulses, in female global Kiss1 knockout (KO) rats and that >90% conditional arcuate Kiss1 KO in newly generated Kiss1-floxed rats completely suppressed LH pulses. These results first provide direct evidence that KNDy neurons are the GnRH pulse generator, and at least 20% of KNDy neurons are sufficient to maintain folliculogenesis via generating GnRH/gonadotropin pulses. © 2020 Proceedings of the National Academy of Sciences of the United States of America. All rights reserved.
英文关键词Conditional Kiss1 KO; Kisspeptin; KNDy rescue; LH pulses; Neurokinin B
语种英语
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180822
作者单位Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan; Section of Mammalian Transgenesis, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8787, Japan; Laboratory of Animal Health, Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, 794-8555, Japan; Section of Viral Vector Development, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8585, Japan
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Nagae M.,Uenoyama Y.,Okamoto S.,et al. Direct evidence that KNDy neurons maintain gonadotropin pulses and folliculogenesis as the GnRH pulse generator[J],2021,118(5).
APA Nagae M..,Uenoyama Y..,Okamoto S..,Tsuchida H..,Ikegami K..,...&Tsukamura H..(2021).Direct evidence that KNDy neurons maintain gonadotropin pulses and folliculogenesis as the GnRH pulse generator.Proceedings of the National Academy of Sciences of the United States of America,118(5).
MLA Nagae M.,et al."Direct evidence that KNDy neurons maintain gonadotropin pulses and folliculogenesis as the GnRH pulse generator".Proceedings of the National Academy of Sciences of the United States of America 118.5(2021).
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