Peripheral administration of SB223412, a selective neurokinin-3 receptor antagonist, suppresses pulsatile luteinizing hormone secretion by acting on the gonadotropin-releasing hormone pulse generator in estrogen-treated ovariectomized female goats

Takuya SASAKI; Tomoya SONODA; Ryoki TATEBAYASHI; Yuri KITAGAWA; Shinya OISHI; Koki YAMAMOTO; Nobutaka FUJII; Naoko INOUE; Yoshihisa UENOYAMA; Hiroko TSUKAMURA; Kei-ichiro MAEDA; Fuko MATSUDA; Yasuhiro MORITA; Shuichi MATSUYAMA; Satoshi OHKURA

doi:10.1262/jrd.2019-145

Original Article

Peripheral administration of SB223412, a selective neurokinin-3 receptor antagonist, suppresses pulsatile luteinizing hormone secretion by acting on the gonadotropin-releasing hormone pulse generator in estrogen-treated ovariectomized female goats

Takuya SASAKI, Tomoya SONODA, Ryoki TATEBAYASHI, Yuri KITAGAWA, Shinya OISHI, Koki YAMAMOTO, Nobutaka FUJII, Naoko INOUE, Yoshihisa UENOYAMA, Hiroko TSUKAMURA, Kei-ichiro MAEDA, Fuko MATSUDA, Yasuhiro MORITA, Shuichi MATSUYAMA, Satoshi OHKURA

Author information

Takuya SASAKI
Laboratory of Animal Production Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
Tomoya SONODA
Laboratory of Animal Production Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
Ryoki TATEBAYASHI
Laboratory of Animal Production Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
Yuri KITAGAWA
Laboratory of Animal Production Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
Shinya OISHI
Laboratory of Bioorganic Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan
Koki YAMAMOTO
Laboratory of Bioorganic Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan
Nobutaka FUJII
Laboratory of Bioorganic Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan
Naoko INOUE
Laboratory of Reproductive Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
Yoshihisa UENOYAMA
Laboratory of Reproductive Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
Hiroko TSUKAMURA
Laboratory of Reproductive Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
Kei-ichiro MAEDA
Laboratory of Theriogenology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
Fuko MATSUDA
Laboratory of Theriogenology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
Yasuhiro MORITA
Laboratory of Animal Production Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
Shuichi MATSUYAMA
Laboratory of Animal Production Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
Satoshi OHKURA
Laboratory of Animal Production Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan

Keywords: Gonadotropin-releasing hormone pulse generator, KNDy neuron, Multiple unit activity, Neurokinin B, Neurokinin 3 receptor

JOURNAL OPEN ACCESS

2020 Volume 66 Issue 4 Pages 351-357

DOI https://doi.org/10.1262/jrd.2019-145

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Abstract

Accumulating evidence suggests that KNDy neurons located in the hypothalamic arcuate nucleus (ARC), which are reported to express kisspeptin, neurokinin B, and dynorphin A, are indispensable for the gonadotropin-releasing hormone (GnRH) pulse generation that results in rhythmic GnRH secretion. The aims of the present study were to investigate the effects of peripheral administration of the neurokinin 3 receptor (NK3R/TACR3, a receptor for neurokinin B) antagonist, SB223412, on GnRH pulse-generating activity and pulsatile luteinizing hormone (LH) secretion in ovariectomized Shiba goats treated with luteal phase levels of estrogen. The NK3R antagonist was infused intravenously for 4 h {0.16 or 1.6 mg/(kg body weight [BW]·4 h)} during which multiple unit activity (MUA) in the ARC was recorded, an electrophysiological technique commonly employed to monitor GnRH pulse generator activity. In a separate experiment, the NK3R antagonist (40 or 200 mg/[kg BW·day]) was administered orally for 7 days to determine whether the NK3R antagonist could modulate pulsatile LH secretion when administered via the oral route. Intravenous infusion of the NK3R antagonist significantly increased the interval of episodic bursts of MUA compared with that of the controls. Oral administration of the antagonist for 7 days also significantly prolonged the interpulse interval of LH pulses. The results of this study demonstrate that peripheral administration of an NK3R antagonist suppresses pulsatile LH secretion by acting on the GnRH pulse generator, suggesting that NK3R antagonist administration could be used to modulate reproductive functions in ruminants.

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