Identification and characterization of a gonadotropin-inhibitory system in the brains of mammals
Identification and characterization of a gonadotropin-inhibitory system in the brains of mammals
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DOI：
10.1073/pnas.0511003103
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发表时间：
2006-02-14
影响因子：
11.1
通讯作者：
Silver, R
中科院分区：
文献类型：
--
作者：
Kriegsfeld, LJ;Mei, DF;Silver, R
成功的生殖需要通过性类固醇的负反馈作用将生殖轴维持在良好的操作范围内。尽管这种自我平衡过程很重要，但我们对神经位点、通路和神经化学物质的理解仍然不完整。在这里，我们揭示了一个神经肽能途径，直接连接性腺类固醇的行动，以调节生殖系统。最近发现了一种能抑制鹌鹑垂体促性腺激素释放的RFamide（rg-Phe-NH 2）肽，并命名为促性腺激素抑制激素（GnIH）。已知鸟类具有与促性腺激素释放激素（GnRH）调节相关的专门适应以优化繁殖（例如，脑光感受器），以及抑制促性腺激素的下丘脑肽的存在可能是或可能不是另一种这样的特化。为了确定GnIH是否作为生殖轴性类固醇调节的信号通路，我们使用免疫组织化学和原位杂交来表征这种肽在仓鼠，大鼠和小鼠中的分布和功能作用。GnIH免疫反应（GnIH-ir）细胞体聚集在下丘脑内侧基底部，在整个CNS中具有明显的投射和终末。体内GnIH给药迅速抑制促黄体激素分泌。此外，GnIH-ir神经元与GnRH细胞形成紧密贴壁，表明GnRH调节的直接手段。最后，GnIH-ir细胞表达雌激素受体-a，并在性腺激素刺激后表现出强烈的立即早期基因表达。两者合计，分布的GnIH传出神经调节生殖行为和神经内分泌，类固醇受体的表达在GnIH-IR核，和GnIH抑制促黄体激素分泌系统调节哺乳动物生殖轴的发现。
Successful reproduction requires maintenance of the reproductive axis within fine operating limits through negative feedback actions of sex steroids. Despite the importance of this homeostatic process, our understanding of the neural loci, pathways, and neurochemicals responsible remain incomplete. Here, we reveal a neuropeptidergic pathway that directly links gonadal steroid actions to regulation of the reproductive system. An RFamide (rg-Phe-NH2) peptide that inhibits gonadotropin release from quail pituitary was recently identified and named gonadotropin-inhibitory hormone (GnIH). Birds are known to have specialized adaptations associated with gonadotropin-releasing hormone (GnRH) regulation to optimize reproduction (e.g., encephalic photo receptors), and the existence of a hypothalamic peptide inhibiting gonadotropins may or may not be another such specialization. To determine whether GnIH serves as a signaling pathway for sex steroid regulation of the reproductive axis, we used immunohistochemistry and in situ hybridization to characterize the distribution and functional role of this pepticle in hamsters, rats, and mice. GnIH-immunoreactive (GnIH-ir) cell bodies are clustered in the mediobasal hypothalamus with pronounced projections and terminals throughout the CNS. In vivo GnIH administration rapidly inhibits luteinizing hormone secretion. Additionally, GnIH-ir neurons form close appositions with GnRH cells, suggesting a direct means of GnRH modulation. Finally, GnIH-ir cells express estrogen receptor-a and exhibit robust immediate early gene expression after gonadal hormone stimulation. Taken together, the distribution of GnIH efferents to neural sites regulating reproductive behavior and neuroendocrine secretions, expression of steroid receptors in GnIH-ir nuclei, and GnIH inhibition of luteinizing hormone secretion indicate the discovery of a system regulating the mammalian reproductive axis.