Direct regulation of postnatal GnRH neurons by the progesterone derivative allopregnanolone in the mouse.
Direct regulation of postnatal GnRH neurons by the progesterone derivative allopregnanolone in the mouse.
复制标题
黄体酮衍生物四氢孕酮对小鼠出生后 GnRH 神经元的直接调节。
作者：
J. Sim;M. Skynner;A. Herbison
性腺类固醇对GnRH神经元的活性发挥关键反馈作用的机制尚不清楚。我们在此研究了孕激素在脑内快速代谢为神经活性类固醇异孕酮后，是否可能调节GnRH神经元的电活动。使用急性脑切片制备，在河豚毒素存在下，对幼年（出生后15-20天）和成年（出生后60-70天）雌性小鼠的GnRH神经元进行全细胞膜片钳记录。黄体酮（1微米）未观察到对GnRH神经元有任何作用（暴露5分钟）。然而，异孕酮（500 nM-1微米）对所有GnRH神经元的基线膜电位产生快速（<1分钟）影响，并显著（P < 0.01）增强其GABA反应高达4倍。GABA(A)受体拮抗剂双丘碱消除了所有的GABA和异孕酮反应。从幼年和成年GnRH神经元中记录的GnRH神经元的异孕酮敏感性没有差异。这些结果为神经类固醇异孕酮对出生后GnRH神经元的直接作用提供了第一个证据，并提出了孕酮水平波动可能影响雌性小鼠这些重要神经元分泌活性的新机制。
The mechanisms through which gonadal steroids exert critical feedback actions upon the activity of the GnRH neurons are not understood. We have examined here whether progesterone may modulate the electrical activity of the GnRH neurons following its rapid metabolism to the neuroactive steroid allopregnanolone within the brain. Using an acute brain slice preparation, whole-cell, patch-clamp recordings were made from GnRH neurons of juvenile (postnatal d 15-20) and adult (postnatal d 60-70) female mice in the presence of tetrodotoxin. Progesterone (1 microM) was not observed to have any actions (up to 5 min exposure) upon GnRH neurons. However, allopregnanolone (500 nM-1 microM) exerted rapid (<1 min) effects upon the baseline membrane potential of all GnRH neurons and also significantly (P < 0.01) enhanced their GABA responses by up to 4-fold. All GABA and allopregnanolone responses were abolished by the GABA(A) receptor antagonist bicuculline. No differences were detected in the allopregnanolone sensitivity of GnRH neurons recorded from juvenile and adult GnRH neurons. These results provide the first evidence for a direct action of the neurosteroid allopregnanolone on postnatal GnRH neurons and suggest a new mechanism through which fluctuating progesterone levels may influence the secretory activity of these important neurons in the female mouse.
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影响因子：
4.8
作者：
A. Lagrange;O. Rønnekleiv;M. Kelly
通讯作者：
A. Lagrange;O. Rønnekleiv;M. Kelly
灵长类动物下丘脑中含有雌激素敏感孕激素受体的神经元的递质含量和传入连接。
影响因子：
4.1
作者：
Leranth,C;MacLusky,NJ;Brown,TJ;Chen,EC;RedmondJr,DE;Naftolin,F
通讯作者：
Naftolin,F
影响因子：
4.8
作者：
Chappell, PE;Lydon, JP;Levine, JE
通讯作者：
Levine, JE
影响因子：
3.6
作者：
Levine, JE
通讯作者：
Levine, JE
黄体酮对促性腺激素释放激素分泌的负反馈作用是由经典黄体酮受体转导的。
DOI：
10.1073/pnas.95.18.10978
发表时间：
1998
影响因子：
11.1
作者：
Skinner,DC;Evans,NP;Delaleu,B;Goodman,RL;Bouchard,P;Caraty,A
通讯作者：
Caraty,A