Direct evidence that KNDy neurons maintain gonadotropin pulses and folliculogenesis as the GnRH pulse generator.

Autor:	Nagae M; Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan., Uenoyama Y; Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan., Okamoto S; Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan., Tsuchida H; Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan., Ikegami K; Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan., Goto T; 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., Majarune S; Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan., Nakamura S; Laboratory of Animal Health, Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime 794-8555, Japan., Sanbo M; Section of Mammalian Transgenesis, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi 444-8787, Japan., Hirabayashi M; Section of Mammalian Transgenesis, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi 444-8787, Japan., Kobayashi K; Section of Viral Vector Development, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan., Inoue N; Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan., Tsukamura H; Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan; htsukamura@nagoya-u.jp.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Feb 02; Vol. 118 (5).
DOI:	10.1073/pnas.2009156118
Abstrakt:	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 k isspeptin (encoded by Kiss1 ), n eurokinin B (encoded by Tac3 ), and dy norphin 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. Competing Interests: The authors declare no competing interest.
Databáze:	MEDLINE
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