dynorphin-kappa opioid receptor signaling partly mediates estrogen negative feedback effect on LH pulses in female rats.

dynorphin-kappa opioid receptor signaling partly mediates estrogen negative feedback effect on LH pulses in female rats.
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DOI:
10.1262/jrd.2012-193
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发表时间:
2013
期刊:
The Journal of reproduction and development
影响因子:
--
通讯作者:
Tsukamura H
Tsukamura H
中科院分区:
其他
文献类型:
--
作者:
Mostari P;Ieda N;Deura C;Minabe S;Yamada S;Uenoyama Y;Maeda K;Tsukamura H

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越来越多的证据表明,弓状核(ARC)、Kispeptin/神经激肽B(NKB)/强啡肽(KNDy)神经元在雌激素对促性腺激素释放激素(GnRH)/黄体生成素(LH)释放的负反馈作用中起作用。本研究旨在确定强啡肽(Dyn)是否参与雌激素对GnRH/LH搏动性释放的负反馈作用。在去卵巢(OVX)雌性大鼠的第三脑室(3V)注射kappa阿片受体(KOR)拮抗剂Nor-BNI(Nor-BNI),观察其对去卵巢(OVX)雌性大鼠黄体生成素(LH)脉搏的影响。注射Nor-BNI、低E2组大鼠的平均黄体生成素浓度和黄体生成素分泌基线水平显著高于赋形剂对照组。另一方面,NOR-BNI治疗不影响去卵巢大鼠的任何黄体生成素脉冲参数,而不是低E2治疗。这些结果表明,Dyn参与了雌激素对GnRH/LH脉冲性释放的负反馈调节。低E_2处理对ARC Pdyn(dyn基因)、Kiss1和Tac2(NKB基因)的表达细胞数无显著影响。治疗对ARC-正中隆起区Pdyn和OPRK1(KOR基因)的mRNA水平也没有影响,但显著增加了ARC-Kisspeptin的免疫反应。这些发现表明,雌激素的负反馈水平通过一种未知的机制抑制ARC KNDy神经元释放Kispeptin,而不影响ARC内Dyn和KOR的表达。综上所述,本研究结果提示,Dyn-KOR信号是雌激素通过减少雌性大鼠GnRH/LH脉冲释放而对GnRH/LH脉冲负反馈作用的一部分。
Accumulating evidence suggests that the arcuate nucleus (ARC) kisspeptin/neurokinin B (NKB)/dynorphin (KNDy) neurons play a role in estrogen negative feedback action on pulsatile gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release. The present study aimed to determine if dynorphin (Dyn) is involved in estrogen negative feedback on pulsatile GnRH/LH release. The effect of the injection of nor-binaltorphimine (nor-BNI), a kappa-opioid receptor (KOR) antagonist, into the third cerebroventricle (3V) on LH pulses was determined in ovariectomized (OVX) adult female rats with/without replacement of negative feedback levels of estradiol (low E2). The mean LH concentrations and baseline levels of LH secretion in nor-BNI-injected, low E2-treated rats were significantly higher compared with vehicle-treated controls. On the other hand, the nor-BNI treatment failed to affect any LH pulse parameters in OVX rats without low E2 treatment. These results suggest that Dyn is involved in the estrogen negative feedback regulation of pulsatile GnRH/LH release. The low E2 treatment had no significant effect on the numbers of ARC Pdyn (Dyn gene)-,Kiss1- and Tac2 (NKB gene)-expressing cells. The treatment also did not affect mRNA levels of Pdyn and Oprk1 (KOR gene) in the ARC-median eminence region, but significantly increased the ARC kisspeptin immunoreactivity. These findings suggest that the negative feedback level of estrogen suppresses kisspeptin release from the ARC KNDy neurons through an unknown mechanism without affecting the Dyn and KOR expressions in the ARC. Taken together, the present result suggests that Dyn-KOR signaling is a part of estrogen negative feedback action on GnRH/LH pulses by reducing the kisspeptin release in female rats.
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