The membrane actions of estrogens can potentiate their lordosis behavior-facilitating genomic actions
The membrane actions of estrogens can potentiate their lordosis behavior-facilitating genomic actions
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DOI：
10.1073/pnas.0404889101
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发表时间：
2004-08-17
影响因子：
11.1
通讯作者：
Pfaff, DW
中科院分区：
文献类型：
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作者：
Kow, LM;Pfaff, DW
雌激素的膜作用可以促进其基因组作用。为了确定这种促进作用是否对雌激素依赖性行为的中枢神经系统机制有任何影响，将卵巢切除的大鼠直接在下丘脑腹膜核中直接接受雌激素的两脉冲治疗。两天后，将每只大鼠给予孕激素，然后测试过遗传学行为，其诱导需要雌激素的基因组作用。当两种脉冲（持续15分钟至2小时，相距5小时）中给出雌激素时，肌病均被诱导。基于对神经母细胞瘤细胞的研究的结果，我们假设雌激素在第一个脉冲中的膜作用将增强第二个雌激素的基因组作用。通过使用膜侵蚀的雌激素证实了这一假设。但是，令人惊讶的是，脉冲的顺序可以逆转，仍然可以实现Lordosis行为诱导。最后，蛋白激酶A或PKC的活化剂是雌激素膜受限脉冲的有效替代物。因此，下丘脑中雌激素诱导的膜作用可以增强其对行为的基因组作用的增强，并可以通过涉及蛋白激酶A和PKC激活的信号通路来介导。
The membrane actions of estrogens can facilitate their genomic actions. To determine whether this facilitation bears on CNS mechanisms for estrogen-dependent behaviors, ovariectomized rats were subjected to a two-pulse treatment of estrogen directly in the hypothalamic ventromedial nucleus. Two days later, each rat was given progesterone and then tested for lordosis behavior, the induction of which requires the genomic actions of estrogen. When estrogen was given in both pulses (15 min to 2 h duration, and 5 h apart) lordosis was induced. Based on results from studies on neuroblastoma cells, we hypothesized that the membrane actions of estrogen in the first pulse would potentiate the genomic actions of estrogen in the second. This hypothesis was confirmed with the use of a membrane-impermeable estrogen. However, surprisingly, the order of the pulses could be reversed and still achieve lordosis behavior induction. Finally, activators of protein kinase A or PKC were effective substitutes for the membrane-limited pulse of estrogen. Thus, estrogen-induced membrane actions in the hypothalamus can potentiate its lordosis-inducing genomic actions on behavior and may be mediated by signaling pathways involving the activation of protein kinase A and PKC.