Participation of growth factor signal transduction pathways in estradiol facilitation of female reproductive behavior
Participation of growth factor signal transduction pathways in estradiol facilitation of female reproductive behavior
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DOI：
10.1210/en.2003-0157
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发表时间：
2003-09-01
期刊：
影响因子：
4.8
通讯作者：
Acosta-Martinez, M
中科院分区：
文献类型：
--
作者：
Etgen, AM;Acosta-Martinez, M
雌二醇（E-2）通过作用于雌激素敏感神经元调节雌性生殖行为（前凸）。我们最近发现，E-2促进前凸行为需要同时激活脑igf - 1受体。本研究证实了这一发现，并试图确定雌激素/ igf - 1引发前凸的下游信号通路。从每日两次E-2注射前1小时开始，每12小时给卵巢切除的大鼠脑室内输注选择性IGF-I受体拮抗剂。如果拮抗剂在整个2天雌激素治疗期间输注，IGF-I受体阻断剂部分抑制前倾，但如果仅在雌激素治疗的第一个或最后12小时给予，则不能。由于E-2和igf可以激活磷脂酰肌醇-3激酶（PI3K）和MAPK，我们按照上述方法注入阻断PI3K和/或MAPK活性的药物。在雌激素启动期间，PI3K抑制剂（wortmannin和LY294002）和MAPK抑制剂（PD98059和U0126）都能部分减轻前凸。如果在雌激素治疗的最后12小时内只注射一次，这些药物都不会改变前凸。当在E-2启动时同时注入wortmannin和PD98059时，前凸行为完全被消除。这些数据表明，E-2和IGF-I激活PI3K和MAPK介导了前凸行为的激素促进。
Estradiol (E-2) regulates female reproductive behavior ( lordosis) by acting on estrogen-sensitive neurons. We recently showed that E-2 facilitation of lordosis behavior requires concurrent activation of brain IGF-I receptors. The present study confirmed this finding and sought to identify the downstream signaling pathways involved in estrogen/IGF-I priming of lordosis. Intracerebroventricular infusions of a selective IGF-I receptor antagonist were administered to ovariectomized rats every 12 h beginning 1 h before the first of two daily E-2 injections. IGF-I receptor blockade partially inhibits lordosis if the antagonist is infused throughout the 2-d estrogen treatment period but not if it is administered only during the first or last 12 h of estrogen treatment. Because E-2 and IGF-can activate phosphatidylinositol-3-kinase (PI3K) and MAPK, we infused agents that block PI3K and/or MAPK activity as described above. Both PI3K inhibitors (wortmannin and LY294002) and MAPK inhibitors (PD98059 and U0126) partially attenuate lordosis when administered during estrogen priming. None of these drugs modifies lordosis if they are infused only once, during the last 12 h of estrogen treatment. When both wortmannin and PD98059 are infused during E-2 priming, lordosis behavior is completely abolished. These data suggest that activation of both PI3K and MAPK by E-2 and IGF-I mediates hormonal facilitation of lordosis behavior.