Chronic peripheral administration of kappa-opioid receptor antagonist advances puberty onset associated with acceleration of pulsatile luteinizing hormone secretion in female rats.
Chronic peripheral administration of kappa-opioid receptor antagonist advances puberty onset associated with acceleration of pulsatile luteinizing hormone secretion in female rats.
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DOI：
10.1262/jrd.2013-046
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Tsukamura H
中科院分区：
文献类型：
--
作者：
Nakahara T;Uenoyama Y;Iwase A;Oishi S;Nakamura S;Minabe S;Watanabe Y;Deura C;Noguchi T;Fujii N;Kikkawa F;Maeda K;Tsukamura H
哺乳动物的青春期是由促性腺激素释放激素（GnRH）分泌的增加来决定的。先前的研究表明，kisspeptin和neurokinin B （NKB）这两种神经肽参与控制青春期的发生。尽管这三种神经肽都分布在弓状kisspeptin神经元中，但我们对另一种关键神经肽dynorphin在控制青春期发病中的作用知之甚少。弓形kisspeptin神经元，也被称为KNDy神经元，最近被认为是GnRH脉冲发生器的内在来源。本研究旨在确定在正常发育的雌性大鼠中，抑制性运动啡-kappa-阿片受体（KOR）信号的衰减是否会触发青春期的开始。本研究还确定了刺激nkb -神经激肽3受体（NK3R）信号传导是否会促进青春期的发生。雌性Wistar-Imamichi大鼠断奶，并在20日龄时腹腔注入充满非双萘哌胺（non - binaltorphine，一种KOR拮抗剂）或senktide（一种NK3R激动剂）的渗透性微型泵。腹腔注射非bni或senktide后第14天，雌性大鼠青春期开始提前，表现为阴道开口和第一次阴道发情。频繁的血液采样显示，在29日龄时，与服用药物的对照组相比，不服用bni显著增加了黄体生成素（LH）的脉搏频率。Senktide倾向于增加这一频率，但其效果无统计学意义。目前的研究结果表明，dynorphin-KOR信号的抑制性输入在正常发育的雌性大鼠青春期前抑制GnRH/LH分泌中起作用，并且dynorphin-KOR信号的衰减和NKB-NK3R信号的增加触发了雌性大鼠青春期的开始。
Puberty in mammals is timed by an increase in gonadotropin-releasing hormone (GnRH) secretion. Previous studies have shown involvement of the two neuropeptides, kisspeptin and neurokinin B (NKB), in controlling puberty onset. Little is known about the role of the other key neuropeptide, dynorphin, in controlling puberty onset, although these three neuropeptides colocalize in the arcuate kisspeptin neurons. The arcuate kisspeptin neuron, which is also referred to as the KNDy neuron, has recently been considered to play a role as an intrinsic source of the GnRH pulse generator. The present study aimed to determine if attenuation of inhibitory dynorphin-kappa-opioid receptor (KOR) signaling triggers the initiation of puberty in normal developing female rats. The present study also determined if stimulatory NKB-neurokinin 3 receptor (NK3R) signaling advances puberty onset. Female Wistar-Imamichi rats were weaned and intraperitoneally implanted with osmotic minipumps filled with nor-binaltorphimine (nor-BNI), a KOR antagonist, or senktide, a NK3R agonist, at 20 days of age. Fourteen days of intraperitoneal infusion of nor-BNI or senktide advanced puberty onset, manifested as vaginal opening and the first vaginal estrus in female rats. Frequent blood sampling showed that nor-BNI significantly increased luteinizing hormone (LH) pulse frequency at 29 days of age compared with vehicle-treated controls. Senktide tended to increase this frequency, but its effect was not statistically significant. The present results suggest that the inhibitory input of dynorphin-KOR signaling plays a role in the prepubertal restraint of GnRH/LH secretion in normal developing female rats and that attenuation of dynorphin-KOR signaling and increase in NKB-NK3R signaling trigger the onset of puberty in female rats.
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DOI：
10.1262/jrd.2012-193
发表时间：
2013
期刊：
The Journal of reproduction and development
影响因子：
--
作者：
Mostari P;Ieda N;Deura C;Minabe S;Yamada S;Uenoyama Y;Maeda K;Tsukamura H
通讯作者：
Tsukamura H
DOI：
10.1073/pnas.1834399100
发表时间：
2003-09-16
影响因子：
11.1
作者：
de Roux, N;Genin, E;Milgrom, E
通讯作者：
Milgrom, E
影响因子：
4.8
作者：
Navarro, V. M.;Gottsch, M. L.;Steiner, R. A.
通讯作者：
Steiner, R. A.
DOI：
10.1073/pnas.0409822102
发表时间：
2005-02-08
影响因子：
11.1
作者：
Shahab, M;Mastronardi, C;Plant, TM
通讯作者：
Plant, TM
影响因子：
5.8
作者：
Gianetti, Elena;Tusset, Cintia;Seminara, Stephanie B.
通讯作者：
Seminara, Stephanie B.