Neurosteroids, trigger of the LH surge.
Neurosteroids, trigger of the LH surge.
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神经素，LH激增的触发因素。
DOI：
10.1016/j.jsbmb.2012.01.008
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发表时间：
2012-08
影响因子：
4.1
通讯作者：
Micevych, Paul
中科院分区：
文献类型：
--
作者：
Kuo, John;Micevych, Paul
我们实验室最近的实验结果与下丘脑星形胶质细胞是中枢神经系统（CNS）介导的雌激素正反馈机制的重要组成部分的观点一致。"星形分泌假说"认为，卵巢雌二醇迅速增加细胞质游离钙浓度（[Ca 2 +] i），促进星形胶质细胞孕酮的合成。这种下丘脑神经孕酮沿着来自卵巢的升高的雌激素允许促性腺激素释放激素（GnRH）的激增释放，从而触发垂体促黄体激素（LH）激增。一个狭窄的范围内的雌二醇刺激孕激素的生产支持一个“关-关-关”的机制，调节从雌激素负反馈到雌激素正反馈的过渡，并再次返回。[Ca2 +] i反应和孕酮合成的快速性支持非基因组的膜起始信号传导机制。在下丘脑星形胶质细胞中，膜相关雌激素受体（mER）通过代谢型谷氨酸受体1a（mGluR1a）的反式激活发出信号，这意味着星形胶质细胞的功能受到周围谷氨酸能神经末梢的影响。尽管存在其他假定的mER，如mER β、STX激活的mER-G α q和G蛋白偶联受体30（GPR30），并参与膜介导的信号传导，但它们对生殖的影响仍然不清楚，因为雌性生殖无论是雌激素正反馈还是脊柱前凸行为都需要mER α。星形分泌假说也与雌激素正反馈的性二态性相一致。在啮齿类动物中，只有青春期后的雌性动物才会表现出这种积极的反馈。从女性培养的下丘脑星形胶质细胞，而不是男性，雌二醇通过增加孕酮的合成。雌激素通过调节雌性星形胶质细胞质膜中mER α的水平来自动调节其自身的信号传导。在雄性星形胶质细胞中，雌二醇诱导的mER α增加减弱，表明膜启动的雌二醇信号传导（MIES）也会减弱。事实上，雌二醇诱导[Ca 2 +] i释放在男性星形胶质细胞，但不刺激孕酮合成所需的水平。使用来自青春期后四个核心基因型（FCG）小鼠的下丘脑星形胶质细胞进行这种性分化的调查。在这个模型中，遗传性别与性腺性别是分离的。我们证明，动物睾丸（XYM和XXM）缺乏雌激素的正反馈，强烈表明，性分化的孕激素合成是由性类固醇环境在早期发展。
Recent experiments from our laboratory are consistent with the idea that hypothalamic astrocytes are critical components of the central nervous system (CNS) mediated estrogen positive feedback mechanism. The “astrocrine hypothesis” maintains that ovarian estradiol rapidly increases free cytoplasmic calcium concentrations ([Ca2+]i) that facilitate progesterone synthesis in astrocytes. This hypothalamic neuroprogesterone along with the elevated estrogen from the ovaries allows for the surge release of gonadotropin-releasing hormone (GnRH) that triggers the pituitary luteinizing hormone (LH) surge. A narrow range of estradiol stimulated progesterone production supports an “off-on-off” mechanism regulating the transition from estrogen negative feedback to estrogen positive feedback, and back again. The rapidity of the [Ca2+]i response and progesterone synthesis support a non-genomic, membrane-initiated signaling mechanism. In hypothalamic astrocytes, membrane-associated estrogen receptors (mERs) signal through transactivation of the metabotropic glutamate receptor type 1a (mGluR1a), implying that astrocytic function is influenced by surrounding glutamatergic nerve terminals. Although other putative mERs, such as mERβ, STX-activated mER-Gαq, and G protein-coupled receptor 30 (GPR30), are present and participate in membrane-mediated signaling, their influence in reproduction is still obscure since female reproduction be it estrogen positive feedback or lordosis behavior requires mERα. The astrocrine hypothesis is also consistent with the well-known sexual dimorphism of estrogen positive feedback. In rodents, only post-pubertal females exhibit this positive feedback. Hypothalamic astrocytes cultured from females, but not males, responded to estradiol by increasing progesterone synthesis. Estrogen autoregulates its own signaling by regulating levels of mERα in the plasma membrane of female astrocytes. In male astrocytes, the estradiol-induced increase in mERα was attenuated, suggesting that membrane-initiated estradiol signaling (MIES) would also be blunted. Indeed, estradiol induced [Ca2+]i release in male astrocytes, but not to levels required to stimulate progesterone synthesis. Investigation of this sexual differentiation was performed using hypothalamic astrocytes from post-pubertal four core genotype (FCG) mice. In this model, genetic sex is uncoupled from gonadal sex. We demonstrated that animals that developed testes (XYM and XXM) lacked estrogen positive feedback, strongly suggesting that the sexual differentiation of progesterone synthesis is driven by the sex steroid environment during early development.
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影响因子：
10.9
作者：
Arnold, Arthur P.;van Nas, Atila;Lusis, Aldons J.
通讯作者：
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作者：
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通讯作者：
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