Marchetti B, Gallo F, Farinella Z, Tirolo C, Testa N, Romeo C, Morale M C
Department of Pharmacology, Medical School, University of Catania, Italy.
Ann N Y Acad Sci. 1998 May 1;840:205-48. doi: 10.1111/j.1749-6632.1998.tb09564.x.
The brain-pituitary-reproductive axis and the brain thymus-lymphoid axis are linked by an array of internal mechanisms of communication that use similar signals (neurotransmitters, peptides, growth factors, hormones) acting on similar recognition targets. Moreover, such communication networks form the basis and control each step and every level of reproductive physiology. This presentation highlights the extent to which endocrine, neural, glial, or immunologically competent cells may achieve their specific functions using common mechanisms, but employing them to different degrees. In particular, this work will focus on LHRH, the chief hormone orchestrating reproductive events. Within the thymus LHRH plays a unique role of immunomodulator, contributing to the sex-dependent changes in immune responsiveness during the estrous-menstrual cycle as well as pregnancy. From the recent cloning and sequencing of lymphocyte LHRH, the expression of LHRH receptor mRNA in lymphocyte, the transduction mechanisms involved, and the steroidogenic sensitivity of the intralymphocyte LHRH system. It would appear that this peptide may act as an immunological response modifier in the brain-pituitary-lymphoid-gonadal axis. The interplay between neuronal, endocrine, and immune compartments is further emphasized in the study of LHRH-astroglial interactions. Astrocytes are able to manufacture a wide variety of signaling agents and can secrete immunoregulatory molecules that influence immune cells, as well as the glial cells themselves. Astroglia and the immortalized hypothalamic LHRH (GT1-1) neurons communicate with an array of mechanisms, via soluble mediators as well as cell-to-cell contacts. Manipulation of astroglial-derived cytokines and nitric oxide (NO) in GT1-1 neuron-astroglia cocultures, underscores a potential cross-talk between different intra/inter-cellular mediators in the dynamic control of LHRH release. Further studies aimed to disclose at a biochemical and a molecular level such bidirectional, informative network will give us new insights into more general issues concerned with the malfunction of the neuroendocrine-immune axis.
脑-垂体-生殖轴和脑-胸腺-淋巴轴通过一系列内部通讯机制相连，这些机制使用作用于相似识别靶点的相似信号（神经递质、肽、生长因子、激素）。此外，这种通讯网络构成了生殖生理学各个步骤和层面的基础并对其进行控制。本报告强调了内分泌、神经、神经胶质或具有免疫功能的细胞在多大程度上可利用共同机制实现其特定功能，但使用程度有所不同。特别是，这项工作将聚焦于促性腺激素释放激素（LHRH），它是协调生殖活动的主要激素。在胸腺内，LHRH发挥着独特的免疫调节作用，在发情-月经周期以及孕期对免疫反应性的性别依赖性变化起作用。从淋巴细胞LHRH最近的克隆和测序、LHRH受体mRNA在淋巴细胞中的表达、所涉及的转导机制以及淋巴细胞内LHRH系统的类固醇生成敏感性来看。似乎这种肽可能在脑-垂体-淋巴-性腺轴中作为免疫反应调节剂发挥作用。在对LHRH-星形胶质细胞相互作用的研究中，进一步强调了神经元、内分泌和免疫部分之间的相互作用。星形胶质细胞能够产生多种信号分子，并能分泌影响免疫细胞以及神经胶质细胞自身的免疫调节分子。星形胶质细胞和永生化下丘脑LHRH（GT1-1）神经元通过一系列机制进行通讯，包括可溶性介质以及细胞间接触。在GT1-1神经元-星形胶质细胞共培养物中对星形胶质细胞衍生的细胞因子和一氧化氮（NO）进行操作，突出了不同细胞内/细胞间介质在LHRH释放动态控制中的潜在相互作用。旨在从生化和分子水平揭示这种双向信息网络的进一步研究，将为我们深入了解与神经内分泌-免疫轴功能失调相关的更普遍问题提供新的见解。
