Göngrich Christina, García-González Diego, Le Magueresse Corentin, Roth Lena C, Watanabe Yasuhito, Burks Deborah J, Grinevich Valery, Monyer Hannah
Department of Clinical Neurobiology, Medical Faculty of Heidelberg, German Cancer Research Center, University of Heidelberg Heidelberg, Germany.
Schaller Research Group on Neuropeptides, German Cancer Research Center, CellNetwork Cluster of Excellence, University of Heidelberg Heidelberg, Germany.
Front Mol Neurosci. 2016 Aug 18;9:65. doi: 10.3389/fnmol.2016.00065. eCollection 2016.
Gap junctions are present in many cell types throughout the animal kingdom and allow fast intercellular electrical and chemical communication between neighboring cells. Connexin-36 (Cx36), the major neuronal gap junction protein, synchronizes cellular activity in the brain, but also in other organs. Here we identify a sex-specific role for Cx36 within the hypothalamic-pituitary-gonadal (HPG) axis at the level of the anterior pituitary gland (AP). We show that Cx36 is expressed in gonadotropes of the AP sustaining their synchronous activity. Cx36 ablation affects the entire downstream HPG axis in females, but not in males. We demonstrate that Cx36-mediated coupling between gonadotropes in the AP supports gonadotropin-releasing hormone-induced secretion of luteinizing hormone. Furthermore, we provide evidence for negative feedback regulation of Cx36 expression in the AP by estradiol. We thus, conclude that hormonally-controlled plasticity of gap junction communication at the level of the AP constitutes an additional mechanism affecting female reproduction.
缝隙连接存在于整个动物界的多种细胞类型中，可实现相邻细胞间快速的细胞间电通信和化学通信。连接蛋白36（Cx36）是主要的神经元缝隙连接蛋白，它不仅能使大脑中的细胞活动同步，也能使其他器官中的细胞活动同步。在此，我们确定了Cx36在下丘脑-垂体-性腺（HPG）轴的垂体前叶水平上具有性别特异性作用。我们发现Cx36在垂体前叶的促性腺细胞中表达，维持其同步活动。Cx36基因敲除会影响雌性动物整个下游HPG轴，但对雄性动物没有影响。我们证明，垂体前叶促性腺细胞之间由Cx36介导的耦合作用支持促性腺激素释放激素诱导的促黄体生成素分泌。此外，我们提供了雌二醇对垂体前叶Cx36表达进行负反馈调节的证据。因此，我们得出结论，垂体前叶水平上由激素控制的缝隙连接通信可塑性构成了影响雌性生殖的另一种机制。
