Estradiol attenuates multiple tetrodotoxin-sensitive sodium currents in isolated gonadotropin-releasing hormone neurons.
Estradiol attenuates multiple tetrodotoxin-sensitive sodium currents in isolated gonadotropin-releasing hormone neurons.
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DOI：
10.1016/j.brainres.2010.05.031
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发表时间：
2010-07-23
期刊：
影响因子：
2.9
通讯作者：
Kuehl-Kovarik, M. Cathleen
中科院分区：
文献类型：
--
作者：
Wang, Yong;Garro, Mona;Kuehl-Kovarik, M. Cathleen
促性腺激素释放激素(GnRH)神经元的分泌是性腺产生配子和激素所必需的。随后，GnRH的释放受到类固醇反馈的调节。然而，类固醇，特别是雌二醇，调节GnRH分泌的机制还知之甚少。我们之前已经证明，雌鼠服用雌二醇可以减少荧光标记的GnRH神经元的内向电流。本研究的目的是探讨钠电流在雌二醇负反馈作用中的作用。对分离的幼年、中年或老年雌性小鼠的GnRH神经元进行电生理学研究。所有的小鼠都被摘除了卵巢；一半的小鼠被替换了雌二醇。在用雌二醇处理的幼年动物的GnRH神经元中，动作电位下的钠电流的幅度显著降低。此外，在体雌二醇显著降低瞬时钠电流幅度，延长钠电流失活时间常数。雌二醇使持续钠电流幅度降低，峰电流电位负移。与从幼年生殖动物的细胞中获得的结果相反，雌二醇并没有显著减弱中年或老年小鼠分离的细胞动作电位背后的钠电流。钠通道可以调节细胞阈值、放电潜伏期和动作电位特性。雌激素降低钠电流幅度提示对GnRH神经元的负反馈，这可能导致细胞兴奋性和激素释放的下调。随着年龄的增长，生殖前期和生殖后期动物体内雌二醇调节的减弱可能会导致激素释放的失调。
Secretion from gonadotropin-releasing hormone (GnRH) neurons is necessary for the production of gametes and hormones from the gonads. Subsequently, GnRH release is regulated by steroid feedback. However, the mechanisms by which steroids, specifically estradiol, modulate GnRH secretion are poorly understood. We have previously shown that estradiol administered to the female mouse decreases inward currents in fluorescently-labeled GnRH neurons. The purpose of this study was to examine the contribution of sodium currents in the negative feedback action of estradiol. Electrophysiology was performed on GnRH neurons dissociated from young, middle-aged, or old female mice. All mice were ovariectomized; half were estradiol replaced. The amplitude of the sodium current underlying the action potential was significantly decreased in GnRH neurons from young estradiol-treated animals. In addition, in vivo estradiol significantly decreased the transient sodium current amplitude, but prolonged the sodium current inactivation time constant. Estradiol decreased the persistent sodium current amplitude, and induced a significant negative shift in peak current potential. In contrast to results obtained from cells from young reproductive animals, estradiol did not significantly attenuate the sodium current underlying the action potential in cells isolated from middle-aged or old mice. Sodium channels can modulate cell threshold, latency of firing, and action potential characteristics. The reduction of sodium current amplitude by estradiol suggests a negative feedback on GnRH neurons, which could lead to a downregulation of cell excitability and hormone release. The attenuation of estradiol regulation in peripostreproductive and postreproductive animals could lead to dysregulated hormone release with advancing age.
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DOI：
10.1073/pnas.84.23.8745
发表时间：
1987-12-01
影响因子：
11.1
作者：
KESNER, JS;WILSON, RC;KNOBIL, E
通讯作者：
KNOBIL, E
影响因子：
--
作者：
Noel, Sekoni D.;Keen, Kim L.;Terasawa, Ei
通讯作者：
Terasawa, Ei
影响因子：
4.8
作者：
Evans, NP;Dahl, GE;Karsch, FJ
通讯作者：
Karsch, FJ
影响因子：
2.9
作者：
HIRUMA, H;SANO, A;KIMURA, F
通讯作者：
KIMURA, F
DOI：
10.1073/pnas.0504270102
发表时间：
2005-10-25
影响因子：
11.1
作者：
Christian, CA;Mobley, JL;Moenter, SM
通讯作者：
Moenter, SM