Inducible Kiss1 knockdown in the hypothalamic arcuate nucleus suppressed pulsatile secretion of luteinizing hormone in male mice

Shiori MINABE; Sho NAKAMURA; Eri FUKUSHIMA; Marimo SATO; Kana IKEGAMI; Teppei GOTO; Makoto SANBO; Masumi HIRABAYASHI; Junko TOMIKAWA; Takuya IMAMURA; Naoko INOUE; Yoshihisa UENOYAMA; Hiroko TSUKAMURA; Kei-Ichiro MAEDA; Fuko MATSUDA

doi:10.1262/jrd.2019-164

Original Article

Inducible Kiss1 knockdown in the hypothalamic arcuate nucleus suppressed pulsatile secretion of luteinizing hormone in male mice

Shiori MINABE, Sho NAKAMURA, Eri FUKUSHIMA, Marimo SATO, Kana IKEGAMI, Teppei GOTO, Makoto SANBO, Masumi HIRABAYASHI, Junko TOMIKAWA, Takuya IMAMURA, Naoko INOUE, Yoshihisa UENOYAMA, Hiroko TSUKAMURA, Kei-Ichiro MAEDA, Fuko MATSUDA

Author information

Shiori MINABE
Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan
Sho NAKAMURA
Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan
Eri FUKUSHIMA
Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan
Marimo SATO
Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan
Kana IKEGAMI
Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan
Teppei GOTO
Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi 444-8787, Japan
Makoto SANBO
Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi 444-8787, Japan
Masumi HIRABAYASHI
Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi 444-8787, Japan
Junko TOMIKAWA
Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan
Takuya IMAMURA
Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Naoko INOUE
Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan
Yoshihisa UENOYAMA
Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan
Hiroko TSUKAMURA
Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi 464-8601, Japan
Kei-Ichiro MAEDA
Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan
Fuko MATSUDA
Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan

Keywords: Adeno-associated virus, Gonadotropin, Gonadotropin-releasing hormone, Kiss1, Metastin

JOURNAL OPEN ACCESS

2020 Volume 66 Issue 4 Pages 369-375

DOI https://doi.org/10.1262/jrd.2019-164

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Abstract

Accumulating evidence suggests that kisspeptin-GPR54 signaling is indispensable for gonadotropin-releasing hormone (GnRH)/gonadotropin secretion and consequent reproductive functions in mammals. Conventional Kiss1 knockout (KO) mice and rats are reported to be infertile. To date, however, no study has investigated the effect of inducible central Kiss1 KO/knockdown on pulsatile gonadotropin release in male mammals. Here we report an in vivo analysis of inducible conditional Kiss1 knockdown male mice. The mice were generated by a bilateral injections of either adeno-associated virus (AAV) vectors driving Cre recombinase (AAV-Cre) or AAV vectors driving GFP (AAV-GFP, control) into the hypothalamic arcuate nucleus (ARC) of Kiss1-floxed male mice, in which exon 3 of the Kiss1 gene were floxed with loxP sites. Four weeks after the AAV-Cre injection, the mice showed a profound decrease in the both number of ARC Kiss1-expressing cells and the luteinizing hormone (LH) pulse frequency. Interestingly, pulsatile LH secretion was apparent 8 weeks after the AAV-Cre injection despite the suppression of ARC Kiss1 expression. The control Kiss1-floxed mice infected with AAV-GFP showed apparent LH pulses and Kiss1 expression in the ARC at both 4 and 8 weeks after the AAV-GFP injection. These results with an inducible conditional Kiss1 knockdown in the ARC of male mice suggest that ARC kisspeptin neurons are responsible for pulsatile LH secretion in male mice, and indicate the possibility of a compensatory mechanism that restores GnRH/LH pulse generation.

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