de Wied D, Diamant M, Fodor M
Rudolf Magnus Institute, Medical Faculty, Utrecht University, The Netherlands.
Front Neuroendocrinol. 1993 Oct;14(4):251-302. doi: 10.1006/frne.1993.1009.
This review of the CNS effects of the neurohypophyseal hormones and related neuropeptides discusses recent data illustrating the significance of these principles in brain function, synthesis, distribution, in particular in extrahypothalamic brain structures, binding sites, and signal transduction. Binding sites for vasopressin of the vascular V1a type have been found in the CNS and there is evidence for the existence of a subtype of the antidiuretic V2 receptor in the brain. Also two types of oxytocin binding sites have been detected. One widely distributed throughout the CNS is comparable to the uterine type receptor and a sexually dimorphic slightly different type is found in the ventromedial nucleus. Vasopressin and oxytocin can be converted to highly selective C-terminal fragments as AVP-(4-9) and OXT-(4-9) and shorter fragments. Conversely they can be acetylated. This almost completely blocks intrinsic activity in bioassays for central and peripheral effects. Such modifications are a good example of the plasticity of a neuropeptide system. For a number of CNS effects of the neurohypophyseal hormones, the whole molecule is required, as it is for their endocrine effects. This is the case for the influence of vasopressin on social communication, temperature regulation, epilepsy, and barrel rotation which may be an animal model of febrile convulsions, and some aspects of the central regulation of the cardiovascular system and for oxytocin on sexual behavior, social communication, and grooming. Nonendocrine C-terminal conversion products seem to exert their effects exclusively on the brain. These neuropeptides modulate learning and memory processes, social recognition, and rewarded behavior. The neuroendocrine and neuropeptide effect of vasopressin and oxytocin and related neuropeptides often exert their CNS effects in an opposite way. Neurochemical and electrophysiological studies suggest that norepinephrine, dopamine, serotonin, and glutamate are the neurotransmitters involved in the influence of the neurohypophyseal hormones and related neuropeptides on brain function. It appears that adequate amounts of vasopressin and oxytocin to induce these effects are released at the appropriate sites of action. It is postulated that the mix of neuropeptides released in the brain in response to environmental changes qualifies the behavioral, neuroendocrine, and immune response and the response of the autonomic nervous and vegetative systems of the organism. Although various other neuropeptides, such as those colocalized in vasopressinergic and oxytocinergic neurons, those produced in pro-opiomelanocortin (POMC) systems, and others, play a role in the modulation of adaptive responses, the neurohypophyseal hormones are unique in that their production sites in the hypothalamus serve the periphery, the pituitary, and the brain.
本综述探讨了神经垂体激素及相关神经肽对中枢神经系统（CNS）的作用，阐述了近期数据，这些数据说明了这些物质在脑功能、合成、分布（特别是下丘脑外脑结构中的分布）、结合位点及信号转导方面的重要性。在中枢神经系统中已发现血管加压素的血管V1a型结合位点，并且有证据表明脑中存在抗利尿V2受体的一种亚型。同时也检测到两种类型的催产素结合位点。一种广泛分布于整个中枢神经系统，类似于子宫型受体，另一种在腹内侧核中发现，具有性别差异，略有不同。血管加压素和催产素可转化为高选择性的C末端片段，如AVP-(4 - 9)和OXT-(4 - 9)以及更短的片段。相反，它们也可以被乙酰化。这几乎完全阻断了对中枢和外周作用进行生物测定时的内在活性。这种修饰是神经肽系统可塑性的一个很好的例子。对于神经垂体激素的许多中枢神经系统作用而言，需要整个分子，就如同其内分泌作用一样。血管加压素对社会交流、体温调节、癫痫以及桶状旋转（可能是热性惊厥的动物模型）的影响，以及心血管系统中枢调节的某些方面，还有催产素对性行为、社会交流和梳理行为的影响，均是如此。非内分泌性的C末端转化产物似乎仅对脑发挥作用。这些神经肽调节学习和记忆过程、社会识别以及奖赏行为。血管加压素和催产素以及相关神经肽的神经内分泌和神经肽作用，其对中枢神经系统的影响往往以相反的方式发挥作用。神经化学和电生理研究表明，去甲肾上腺素、多巴胺、5-羟色胺和谷氨酸是参与神经垂体激素及相关神经肽对脑功能影响的神经递质。似乎在适当的作用位点释放了足够量的血管加压素和催产素以诱导这些效应。据推测，大脑中响应环境变化而释放的神经肽混合物决定了行为、神经内分泌和免疫反应以及机体自主神经和植物神经系统的反应。尽管各种其他神经肽，如那些与血管加压素能和催产素能神经元共定位的神经肽、在促肾上腺皮质激素原（POMC）系统中产生的神经肽等，在调节适应性反应中发挥作用，但神经垂体激素的独特之处在于它们在下丘脑的产生部位同时服务于外周、垂体和脑。
