Insulin-like growth factor-I regulates LH release by modulation of kisspeptin and NMDA-mediated neurotransmission in young and middle-aged female rats.
Insulin-like growth factor-I regulates LH release by modulation of kisspeptin and NMDA-mediated neurotransmission in young and middle-aged female rats.
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DOI：
10.1210/en.2013-1682
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发表时间：
2014-03
期刊：
影响因子：
4.8
通讯作者：
G. Neal-Perry;Dachun Yao;Jun Shu;Yan Sun;A. M. Etgen
中科院分区：
文献类型：
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作者：
G. Neal-Perry;Dachun Yao;Jun Shu;Yan Sun;A. M. Etgen
本研究探讨了潜在的机制，年龄和IGF-I受体（IGF-Ir）信号在神经内分泌下丘脑影响雌二醇的正反馈效应GnRH神经元激活和kisspeptin和N-甲基-D-天冬氨酸（NMDA）诱导的LH释放和丰富的NMDA受体亚基Nr 1和Nr 2b和Kiss 1 r转录和蛋白质在年轻和中年雌性大鼠下丘脑。我们将溶媒、IGF-I或JB-1（一种IGF-Ir的选择性拮抗剂）输注到卵巢切除雌性大鼠的第三脑室中，雌性大鼠用雌二醇或溶媒致敏，并注射溶媒、kisspeptin（3或30 nmol/kg）或NMDA（15或30 mg/kg）。无论剂量如何，NMDA和kisspeptin导致年轻女性比中年女性显著更多的LH释放，GnRH/c-Fos共标记和c-Fos免疫反应细胞。雌激素启动显着增加Kiss 1 r，Nr 1和Nr 2b受体转录和蛋白质丰度在年轻的，但不是中年女性下丘脑。JB-1减弱kisspeptin和NMDA诱导的LH释放，GnRH/c-Fos和c-Fos细胞的数量，以及年轻女性中Kiss 1 r，Nr 1和Nr 2b转录物和蛋白质丰度在中年女性中观察到的水平。IGF-I显著增强NMDA和kisspeptin诱导的中年女性LH释放，而不增加GnRH/c-Fos或c-Fos免疫反应细胞的数量。IGF-I输注中年女性也增加Kiss 1 r，Nr 1和Nr 2b蛋白和转录水平相当于年轻的雌二醇引发的女性。这些研究结果表明，年龄相关的变化雌二醇调节的反应兴奋性输入谷氨酸和kisspeptin反映减少IGF-Ir信号。
This study investigated potential mechanisms by which age and IGF-I receptor (IGF-Ir) signaling in the neuroendocrine hypothalamus affect estradiol-positive feedback effects on GnRH neuronal activation and on kisspeptin and N-methyl-D-aspartate (NMDA)-induced LH release and on the abundance of NMDA receptor subunits Nr1 and Nr2b and Kiss1r transcript and protein in the hypothalamus of young and middle-aged female rats. We infused vehicle, IGF-I, or JB-1, a selective antagonist of IGF-Ir, into the third ventricle of ovariectomized female rats primed with estradiol or vehicle and injected with vehicle, kisspeptin (3 or 30 nmol/kg), or NMDA (15 or 30 mg/kg). Regardless of dose, NMDA and kisspeptin resulted in significantly more LH release, GnRH/c-Fos colabeling, and c-Fos immunoreative cells in young than in middle-aged females. Estradiol priming significantly increased Kiss1r, Nr1, and Nr2b receptor transcript and protein abundance in young but not middle-aged female hypothalamus. JB-1 attenuated kisspeptin and NMDA-induced LH release, numbers of GnRH/c-Fos and c-Fos cells, and Kiss1r, Nr1, and Nr2b transcript and protein abundance in young females to levels observed in middle-aged females. IGF-I significantly enhanced NMDA and kisspeptin-induced LH release in middle-aged females without increasing numbers of GnRH/c-Fos or c-Fos immunoreactive cells. IGF-I infusion in middle-aged females also increased Kiss1r, Nr1, and Nr2b protein and transcript to levels that were equivalent to young estradiol-primed females. These findings indicate that age-related changes in estradiol-regulated responsiveness to excitatory input from glutamate and kisspeptin reflect reduced IGF-Ir signaling.