Interactions between kisspeptin and neurokinin B in the control of GnRH secretion in the female rat

Interactions between kisspeptin and neurokinin B in the control of GnRH secretion in the female rat
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DOI:
10.1152/ajpendo.00517.2010
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发表时间:
2011-01-01
影响因子:
5.1
通讯作者:
Steiner, Robert A.
Steiner, Robert A.
中科院分区:
医学2区
文献类型:
--
作者:
Navarro, Victor M.;Castellano, Juan M.;Steiner, Robert A.

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Navarro VM,Castellano JM,McConkey SM,Pineda R,Ruiz-Pino F,Pinilla L,克利夫顿DK,Tena-Sempere M,Steiner RA. Kisspeptin和神经激肽B在雌性大鼠GnRH分泌调控中的相互作用Am J Physiol Endocrinol Metab 300:E202-E210,2011。首次发表于2010年11月2日; doi:10.1152/ajpendo.00517.2010.-神经激肽B(NKB)及其同源受体神经激肽3(NK 3 R)在生殖过程中起着关键作用。在弓状核(Arc)的神经元中,NKB和NK 3R与强啡肽(Dyn)和kisspeptin(Kiss 1)基因共表达。然而,NKB作为kisspeptin和强啡肽的共递质的作用机制仍然知之甚少。我们探索了NKB在雌性大鼠LH分泌控制中的作用如下。1)我们研究了NKB激动剂(senktide,600 pmol,注入侧脑室)对黄体生成素(LH)分泌的影响。在生理水平的雌二醇(E2)存在下,参克肽诱导血清LH水平显著升高,Arc中表达c-fos的Kiss 1神经元数量增加10倍(两者均P < 0.01)。2)我们绘制了NKB和NK 3R mRNA在中央前脑中的分布,发现两者都广泛表达,在控制生殖的几个下丘脑核团(包括Arc)中表达强烈。3)我们研究了E(2)对NKB和NK 3R mRNA在Arc中表达的影响,发现E(2)抑制这两种基因的表达(P < 0.01),并且NKB和NK 3R的表达在发情前期的下午达到最低点(当循环中E(2)水平高时)。这些结果表明,NKB/NK 3R信号在大鼠Arc的Kiss 1/NKB/Dyn-producing神经元中具有关键作用,在促性腺激素释放激素(GnRH)/LH分泌的控制和E2依赖性负反馈的调节中具有关键作用。
Navarro VM, Castellano JM, McConkey SM, Pineda R, Ruiz-Pino F, Pinilla L, Clifton DK, Tena-Sempere M, Steiner RA. Interactions between kisspeptin and neurokinin B in the control of GnRH secretion in the female rat. Am J Physiol Endocrinol Metab 300: E202-E210, 2011. First published November 2, 2010; doi:10.1152/ajpendo.00517.2010.-Neurokinin B (NKB) and its cognate receptor neurokinin 3 (NK3R) play a critical role in reproduction. NKB and NK3R are coexpressed with dynorphin (Dyn) and kisspeptin (Kiss1) genes in neurons of the arcuate nucleus (Arc). However, the mechanisms of action of NKB as a cotransmitter with kisspeptin and dynorphin remain poorly understood. We explored the role of NKB in the control of LH secretion in the female rat as follows. 1) We examined the effect of an NKB agonist (senktide, 600 pmol, administered into the lateral cerebral ventricle) on luteinizing hormone (LH) secretion. In the presence of physiological levels of estradiol (E(2)), senktide induced a profound increase in serum levels of LH and a 10-fold increase in the number of Kiss1 neurons expressing c-fos in the Arc (P < 0.01 for both). 2) We mapped the distribution of NKB and NK3R mRNAs in the central forebrain and found that both are widely expressed, with intense expression in several hypothalamic nuclei that control reproduction, including the Arc. 3) We studied the effect of E(2) on the expression of NKB and NK3R mRNAs in the Arc and found that E(2) inhibits the expression of both genes (P < 0.01) and that the expression of NKB and NK3R reaches its nadir on the afternoon of proestrus (when circulating levels of E(2) are high). These observations suggest that NKB/NK3R signaling in Kiss1/NKB/Dyn-producing neurons in the Arc has a pivotal role in the control of gonadotropin-releasing hormone (GnRH)/LH secretion and its regulation by E(2)-dependent negative feedback in the rat.