SB223412, a neurokinin-3 receptor-selective antagonist, suppresses testosterone secretion in male guinea pigs

Nakamura, Sho; Ito, Yoshiko; Yamamoto, Koki; Takahashi, Chudai; Dai, Mingdao; Tanahashi, Miyu; Uenoyama, Yoshihisa; Tsukamura, Hiroko; Oishi, Shinya; Maeda, Kei‐ichiro; Matsuda, Fuko

doi:10.1016/j.theriogenology.2017.07.053

Cited by 12 publications

(10 citation statements)

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“…The administration of kisspeptin resulted in strong stimulation of GnRH and gonadotropin releases in rodents, ruminants and primates . Further, existence of kisspeptin neurons in hypothalamus are reported in wide variety of mammalian species . All these results implicate that kisspeptin is a common factor between mammals that primarily controls gonadotropin release including feedback regulation by estrogen.…”

Section: Gnrh and Kisspeptinmentioning

confidence: 87%

Role of kisspeptin neurons as a GnRH surge generator: Comparative aspects in rodents and non‐rodent mammals

Matsuda

Ohkura

Magata

et al. 2019

J of Obstet and Gynaecol

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Ovulation is an essential phenomenon for reproduction in mammalian females along with follicular growth. It is well established that gonadal function is controlled by the neuroendocrine system called the hypothalamus-pituitary-gonadal (HPG) axis. Gonadotropin-releasing hormone (GnRH) neurons, localized in the hypothalamus, had been considered to be the head in governing the HPG axis for a long time until the discovery of kisspeptin. In females, induction of ovulation and folliculogenesis has been linked to a surge mode and pulse mode of GnRH releases, respectively. The mechanisms of how the two modes of GnRH are differently regulated had long remained elusive. The discovery of kisspeptin neurons, distributed in two hypothalamic nuclei, such as the arcuate nucleus in the caudal hypothalamus and preoptic area or the anteroventral periventricular nucleus in the rostral hypothalamic regions, and analyses of the detailed functions of kisspeptin neurons have led marked progress on the understanding of different mechanisms regulating GnRH surges (ovulation) and GnRH pulses (folliculogenesis). The present review will focus on the role of kisspeptin neurons as the GnRH surge generator, including the sexual differentiation of the surge generation system and factors that regulate the surge generator. Comparative aspects between mammalian species are especially focused on.

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Section: Gnrh and Kisspeptinmentioning

confidence: 87%

Role of kisspeptin neurons as a GnRH surge generator: Comparative aspects in rodents and non‐rodent mammals

Matsuda

Ohkura

Magata

et al. 2019

J of Obstet and Gynaecol

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“…Plasma testosterone concentrations were determined by an enzyme immunoassay as described previously [ 29 ]. Testosterone was measured after diethyl-ether extraction, followed by an overnight incubation with sheep anti-testosterone antibody (1: 60,000, GDN #250, kindly donated by Dr GD Niswander, Colorado University, CO, USA) at 4°C in 96-well plates pre-coated with rabbit anti-sheep IgG antibody (0.5 µg/100 µl/well, #613-4128, Rockland Immunochemicals, PA. USA).…”

Section: Methodsmentioning

confidence: 99%

Section: Lh and Testosterone Assaysmentioning

confidence: 99%

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

Minabe

Nakamura

Fukushima

et al. 2020

Journal of Reproduction and Development

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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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“…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%

“…To achieve this, the effects of peripheral administration of NK3R antagonists on reproduction and mechanism mediating the effect should first be clarified. Previous studies have demonstrated that oral administration of SB223412, a selective NK3R antagonist, suppresses testosterone secretion in male dogs [ 21 ] and guinea pigs [ 20 ]. Peripherally administered ESN234, another NK3R antagonist, was also indicated to suppress pulsatile LH secretion in ovariectomized (OVX) ewes and decrease plasma estrogen levels, both in female monkeys [ 22 ] and in women [ 30 ].…”

mentioning

confidence: 99%

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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SB223412, a neurokinin-3 receptor-selective antagonist, suppresses testosterone secretion in male guinea pigs

Cited by 12 publications

References 46 publications

Role of kisspeptin neurons as a GnRH surge generator: Comparative aspects in rodents and non‐rodent mammals

Role of kisspeptin neurons as a GnRH surge generator: Comparative aspects in rodents and non‐rodent mammals

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

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

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