Dreifuss J J
Ann N Y Acad Sci. 1975 Feb 21;248:184-201. doi: 10.1111/j.1749-6632.1975.tb34185.x.
The available evidence suggests that hormones and neurophysins are associated exclusively with the neurosecretory granules, each of which contains approximately 6 times 10-4 molecules of each. Hormones and carrier proteins are complexed within the granules and the complexes are densely packed. The processes that keep the intragranular space in osmotic equilibrium with the axoplasm require further study. Freeze-fracture data, as well as studies in which histochemical methods for the detection of glycoproteins were used, suggest that the intragranular aspect of the granule membrane mostly resembles the extracellular half of the plasma membrane; on the other hand, the cytoplasmic aspects of plasma and granule membrane have similar characteristics, which may be important in permitting membrane fusion to take place prior to secretion. Little is known about the molecular species involved in this interaction between granule and plasma membrane, except that calcium is a cofactor in this process. Release is triggered in vivo by propagated action potentials which cause an influx of calcium into the secretory endings. Newly formed granules, and other granules located at the periphery of the endings are preferentially released. Irrespective of the type of stimulation of secretion, release involves the diffusion into the extracellular space of granule core constituents. The best evidence so far in support of this view comes from ultrastructural studies showing images of exocytosis, as well as from biochemical studies demonstrating that hormones and carrier proteins are secreted concomitantly in a great variety of experimental or clinical conditions, without an associated release of granule membrane constituents or of enzymes of cytoplasmic origin. Recovery mechanisms following secretion require new synthesis of granule constituents and restoration of the resting internal concentrations of potassium, sodium, and calcium. Membrane surface area is restored following exocytosis by compensatory endocytosis which involves indiscriminate uptake of extracellular medium into the secretory axon terminals. While much progress has been made in research on the cellular and subcellular processes that take place in neurons which produce, store, and secrete neurohypophyseal hormones and their carrier proteins, neurophysins, many pressing questions remain to be answered. New developments, such as organ culture of supraoptic nuclei94-96 and the recent isolation of a clone of mouse hypothalamic cells capable of synthesizing vasopressin and neurophysin,97 will hopefully allow some of these problems to be solved in the future.
现有证据表明，激素和神经垂体素仅与神经分泌颗粒相关联，每个颗粒大约含有6×10⁻⁴个分子的激素和神经垂体素。激素和载体蛋白在颗粒内形成复合物，且这些复合物紧密堆积。维持颗粒内空间与轴浆渗透压平衡的过程尚需进一步研究。冷冻断裂数据以及使用检测糖蛋白的组织化学方法进行的研究表明，颗粒膜的颗粒内面大多类似于质膜的细胞外半层；另一方面，质膜和颗粒膜的胞质面具有相似特征，这在分泌前允许膜融合方面可能很重要。除了钙是这一过程的辅助因子外，对于参与颗粒与质膜之间这种相互作用的分子种类知之甚少。在体内，传播的动作电位引发释放，动作电位导致钙流入分泌末梢。新形成的颗粒以及位于末梢周边的其他颗粒优先被释放。无论分泌刺激的类型如何，释放都涉及颗粒核心成分扩散到细胞外空间。目前支持这一观点的最佳证据来自显示胞吐作用图像的超微结构研究，以及生化研究，这些研究表明在各种实验或临床条件下，激素和载体蛋白是伴随分泌的，而没有颗粒膜成分或胞质来源的酶的相关释放。分泌后的恢复机制需要新合成颗粒成分，并恢复钾、钠和钙的静息内部浓度。胞吐作用后，通过补偿性内吞作用恢复膜表面积，补偿性内吞作用涉及将细胞外介质无差别地摄取到分泌轴突末梢中。虽然在研究产生、储存和分泌神经垂体激素及其载体蛋白、神经垂体素的神经元中发生的细胞和亚细胞过程方面已经取得了很大进展，但许多紧迫问题仍有待解答。新的进展，如视上核的器官培养94 - 96以及最近分离出能够合成加压素和神经垂体素的小鼠下丘脑细胞克隆97，有望在未来解决其中一些问题。
