Korf H W, Schomerus C, Stehle J H
Dr. Senckenbergische Anatomie, Anatomisches Institut II, Johann Wolfgang Goethe-Universität, Frankfurt.
Adv Anat Embryol Cell Biol. 1998;146:1-100. doi: 10.1007/978-3-642-58932-4.
The vertebrate pineal organ rhythmically synthesizes and secretes melatonin during nighttime and forms an essential component of the photoneuroendocrine system which allows humans and animals to measure and keep the time. Regulation of the melatonin biosynthesis depends on signals from photoreceptors perceiving and transmitting environmental light stimuli and endogenous oscillators generating a circadian rhythm which is independent from any environmental time cue (zeitgeber). In nonmammalian species the photoreceptors responsible for regulating melatonin biosynthesis reside within the pineal organ itself. In several nonmammalian species (e.g., lamprey, zebra fish, house sparrow, chicken) the pineal organ is also capable of generating circadian rhythms and thus serves all key functions of the photoneuroendocrine system: photoreception, endogenous rhythm generation, and production of neurohormones. These may even be accomplished by a single "photoneuroendocrine" cell. In mammals the pineal organ has lost both the direct light sensitivity and the capacity of generating circadian rhythms, and melatonin biosynthesis is regulated by retinal photoreceptors and a circadian oscillator located in the suprachiasmatic nucleus of the hypothalamus. Due to this spatial separation the photoneuroendocrine system of mammals comprises neuronal and neuroendocrine pathways which interconnect its components. The neuronal pathways involve circuits of both the central and the peripheral nervous systems, and as an important final link noradrenergic sympathetic nerve fibers. The suprachiasmatic nucleus appears as a major target of melatonin in mammals. The pineal hormone may thus be involved in a feedback loop of the mammalian photoneuroendocrine system. The present comparative contribution considers, after a short survey of classical findings on the phylogenetic development and the gross anatomy of the pineal complex, cytoevolutionary and cell biological aspects of the various types of pinealocytes as well as the afferent and efferent innervation of the pineal organ (pinealofugal and pinealopetal neuronal pathways). Moreover, emphasis is placed on receptor mechanisms, second messenger systems (Ca2+ and cyclic AMP), transcription factors (e.g, CREB and ICER), and their roles for regulation of melatonin biosynthesis. Finally, the action, targets, and receptors of melatonin are dealt with. The synoptic approach of this contribution, which combines anatomical and ultrastructural findings with cell and molecular biological results, confirms the functional significance of the melatonin-synthesizing pineal organ as an important component of the photoneuroendocrine system and stresses the importance of this organ as a model to study signal transduction mechanisms both in photoreceptors and in neuroendocrine cells.
脊椎动物的松果体在夜间有节奏地合成并分泌褪黑素，它是光神经内分泌系统的重要组成部分，使人类和动物能够测量并保持时间。褪黑素生物合成的调节取决于来自光感受器的信号，这些光感受器感知并传递环境光刺激，以及内源性振荡器产生的昼夜节律，该节律独立于任何环境时间线索（授时因子）。在非哺乳类物种中，负责调节褪黑素生物合成的光感受器位于松果体自身内部。在一些非哺乳类物种（如七鳃鳗、斑马鱼、家麻雀、鸡）中，松果体也能够产生昼夜节律，因此具备光神经内分泌系统的所有关键功能：光感受、内源性节律产生以及神经激素的分泌。这些功能甚至可能由单个“光神经内分泌”细胞来完成。在哺乳动物中，松果体已经失去了直接的光敏感性和产生昼夜节律的能力，褪黑素的生物合成由视网膜光感受器和位于下丘脑视交叉上核的昼夜振荡器调节。由于这种空间上的分离，哺乳动物的光神经内分泌系统由相互连接其各个组成部分的神经元和神经内分泌途径构成。神经元途径涉及中枢神经系统和外周神经系统的回路，并且作为重要的最终环节，还有去甲肾上腺素能交感神经纤维。视交叉上核似乎是哺乳动物中褪黑素的主要作用靶点。因此，松果体激素可能参与了哺乳动物光神经内分泌系统的反馈回路。本比较性论述在简要概述松果体复合体系统发育和大体解剖的经典研究结果之后，考虑了各种类型松果体细胞的细胞进化和细胞生物学方面，以及松果体的传入和传出神经支配（松果体传出和松果体传入神经元途径）。此外，重点阐述了受体机制、第二信使系统（Ca2+和环磷酸腺苷）、转录因子（如CREB和ICER）及其在褪黑素生物合成调节中的作用。最后，论述了褪黑素的作用、靶点和受体。本论述采用综合方法，将解剖学和超微结构研究结果与细胞和分子生物学结果相结合，证实了合成褪黑素的松果体作为光神经内分泌系统重要组成部分的功能意义，并强调了该器官作为研究光感受器和神经内分泌细胞信号转导机制模型的重要性。
