Peripheral administration of κ-opioid receptor antagonist stimulates gonadotropin-releasing hormone pulse generator activity in ovariectomized, estrogen-treated female goats

Sasaki, Takuya; Ito, Daisuke; Sonoda, Tomoya; Morita, Yasuhiro; Wakabayashi, Yoshihiro; Yamamura, Takashi; Okamura, Hiroaki; Oishi, Shinya; Noguchi, Taro; Fujii, Nobutaka; Uenoyama, Yoshihisa; Tsukamura, Hiroko; Maeda, Kei‐ichiro; Matsuda, Fuko; Ohkura, Satoshi

doi:10.1016/j.domaniend.2018.12.011

Cited by 17 publications

(10 citation statements)

References 37 publications

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“…Plasma LH concentrations were determined by a double-antibody radioimmunoassay, as previously described [ 18 ]. For 50-µl plasma samples, the lowest detectable LH concentration was 0.098 ng/ml, and the intra- and inter-assay coefficients of variation were 6.2% at 3.14 ng/ml and 7.3% at 3.11 ng/ml, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…In Experiment 1, the MUA volley interval was used to evaluate GnRH pulse generator activity. When the difference between the values of two consecutive points exceeded twice the standard deviation calculated during the baseline period before starting the blood collection, the point was designated as the beginning of an MUA volley [ 18 ]. The mean MUA volley interval was calculated for each animal, and then each group in each treatment.…”

Section: Methodsmentioning

confidence: 99%

“…KNDy neuropeptides like NKB and dynorphin A, as well as their respective agonists and antagonists, have attracted considerable interest as pharmacological regulators for use in the artificial control of reproductive functions. Previous studies have demonstrated that agonists and antagonists of KNDy neuropeptide affect gonadotropin and gonadal steroid secretion in mammals, including domestic animals like cattle, goats, and sheep [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ].…”

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confidence: 99%

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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

Sasaki

Sonoda

Tatebayashi

et al. 2020

Journal of Reproduction and Development

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Peripheral administration of SB223412, a selective neurokinin-3 receptor antagonist, suppresses 1 pulsatile luteinizing hormone secretion by acting on the gonadotropin-releasing hormone pulse 2 generator in estrogen-treated ovariectomized female goats 3 4 Abstract (236/250 words) 24Accumulating evidence suggests that KNDy neurons located in the hypothalamic arcuate nucleus (ARC), 25 which are reported to express kisspeptin, neurokinin B, and dynorphin A, are indispensable for the 26 gonadotropin-releasing hormone (GnRH) pulse generation that results in rhythmic GnRH secretion. The 27 aims of the present study were to investigate the effects of peripheral administration of the neurokinin 28 3 receptor (NK3R/TACR3, a receptor for neurokinin B) antagonist, SB223412, on GnRH pulse-29 generating activity and pulsatile luteinizing hormone (LH) secretion in ovariectomized Shiba goats 30 treated with luteal phase levels of estrogen. The NK3R antagonist was infused intravenously for 4 h 31 {0.16 or 1.6 mg/(kg body weight [BW]·4 h)} during which multiple unit activity (MUA) in the ARC 32 was recorded, an electrophysiological technique commonly employed to monitor GnRH pulse generator 33 activity. In a separate experiment, the NK3R antagonist (40 or 200 mg/[kg BW·day]) was administered 34 orally for 7 days to determine whether the NK3R antagonist could modulate pulsatile LH secretion when 35 administered via the oral route. Intravenous infusion of the NK3R antagonist significantly increased the 36 interval of episodic bursts of MUA compared with that of the controls. Oral administration of the 37 antagonist for 7 days also significantly prolonged the interpulse interval of LH pulses. The results of 38this study demonstrate that peripheral administration of an NK3R antagonist suppresses pulsatile LH 39 secretion by acting on the GnRH pulse generator, suggesting that NK3R antagonist administration could 40 be used to modulate reproductive functions in ruminants. 41

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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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

Sasaki

Sonoda

Tatebayashi

et al. 2020

Journal of Reproduction and Development

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“…These findings suggest that dynorphin-KOR signaling and NKB-NK3R signaling play a role in determining the frequency of GnRH pulse generator activities. Furthermore, central or peripheral administration of dynorphin or NK3R antagonists (SB223412 and SB222200) suppressed LH pulses, whereas KOR antagonists (nor-BNI and PF-4455242); NKB, an NK3R agonist (senktide); and kisspeptin stimulated LH pulses in several mammalian species, such as rodents ( Gottsch et al, 2004 ; Irwig et al, 2004 ; Kinoshita et al, 2005 ; Messager et al, 2005 ; Pheng et al, 2009 ; Navarro et al, 2011 ; Mostari et al, 2013 ; Ruiz-Pino et al, 2015 ) and ruminants ( Messager et al, 2005 ; Ohkura et al, 2009 ; Sakamoto et al, 2012 ; Tanaka et al, 2012 ; Goodman et al, 2013 ; Naniwa et al, 2013 ; Yamamura et al, 2015 ; Nakamura et al, 2017 ; Sasaki et al, 2019 , 2020 ).…”

Section: Kisspeptin/neurokinin B/dynorphin Neurons As An Intrinsic Re...mentioning

confidence: 99%

Opioidergic pathways and kisspeptin in the regulation of female reproduction in mammals

et al. 2022

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Endogenous opioid peptides have attracted attention as critical neuropeptides in the central mechanism regulating female reproduction ever since the discovery that arcuate dynorphin neurons that coexpress kisspeptin and neurokinin B (NKB), which are also known as kisspeptin/neurokinin B/dynorphin (KNDy) neurons, play a role as a master regulator of pulsatile gonadotropin-releasing hormone (GnRH) release in mammals. In this study, we first focus on the role of dynorphin released by KNDy neurons in the GnRH pulse generation. Second, we provide a historical overview of studies on endogenous opioid peptides. Third, we discuss how endogenous opioid peptides modulate tonic GnRH/gonadotropin release in female mammals as a mediator of inhibitory internal and external cues, such as ovarian steroids, nutritional status, or stress, on reproduction. Then, we discuss the role of endogenous opioid peptides in GnRH surge generation in female mammals.

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“…Indeed, a central administration of neurokinin B facilitated the frequency of the MUA volley, which is corresponding the GnRH pulse generator activity, and the frequency was lowered by a central administration of dynorphin A and increased by nor-binaltorphimine (nor-BNI), a κ-opioid receptor antagonist, in female goats ( 13 ). Peripheral administrations of PF-4455242, another κ-opioid receptor antagonist, facilitated and SB223412, an NK3 receptor antagonist, suppressed LH pulses in female goats ( 119 , 120 ). Similarly, a central administration of neurokinin B or nor-BNI facilitated and SB222200, another NK3 receptor antagonist, suppressed LH pulses in ewes ( 121 ).…”

Section: Roles Of Kisspeptin Neurokinin B and Dynorphin A In The Mechanism Controlling Gnrh Pulse Generationmentioning

confidence: 99%

Role of KNDy Neurons Expressing Kisspeptin, Neurokinin B, and Dynorphin A as a GnRH Pulse Generator Controlling Mammalian Reproduction

et al. 2021

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Increasing evidence accumulated during the past two decades has demonstrated that the then-novel kisspeptin, which was discovered in 2001, the known neuropeptides neurokinin B and dynorphin A, which were discovered in 1983 and 1979, respectively, and their G-protein-coupled receptors, serve as key molecules that control reproduction in mammals. The present review provides a brief historical background and a summary of our recent understanding of the roles of hypothalamic neurons expressing kisspeptin, neurokinin B, and dynorphin A, referred to as KNDy neurons, in the central mechanism underlying gonadotropin-releasing hormone (GnRH) pulse generation and subsequent tonic gonadotropin release that controls mammalian reproduction.

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Peripheral administration of κ-opioid receptor antagonist stimulates gonadotropin-releasing hormone pulse generator activity in ovariectomized, estrogen-treated female goats

Cited by 17 publications

References 37 publications

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

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

Opioidergic pathways and kisspeptin in the regulation of female reproduction in mammals

Role of KNDy Neurons Expressing Kisspeptin, Neurokinin B, and Dynorphin A as a GnRH Pulse Generator Controlling Mammalian Reproduction

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