Hrabovszky E, Liposits Z
Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
J Neuroendocrinol. 2008 Jun;20(6):743-51. doi: 10.1111/j.1365-2826.2008.01719.x.
L-glutamate, the main excitatory neurotransmitter, influences virtually all neurones of the neuroendocrine hypothalamus via synaptic mechanisms. Vesicular glutamate transporters (VGLUT1-3), which selectively accumulate L-glutamate into synaptic vesicles, provide markers with which to visualise glutamatergic neurones in histological preparations; excitatory neurones in the endocrine hypothalamus synthesise the VGLUT2 isoform. Results of recent dual-label in situ hybridisation studies indicate that glutamatergic neurones in the preoptic area and the hypothalamic paraventricular, supraoptic and periventricular nuclei include parvocellular and magnocellular neurosecretory neurones which secrete peptide neurohormones into the bloodstream to regulate endocrine functions. Neurosecretory terminals of GnRH, TRH, CRF-, somatostatin-, oxytocin- and vasopressin-secreting neurones contain VGLUT2 immunoreactivity, suggesting the co-release of glutamate with hypophysiotrophic peptides. The presence of VGLUT2 also indicates glutamate secretion from non-neuronal endocrine cells, including gonadotrophs and thyrotrophs of the anterior pituitary. Results of in vitro studies show that ionotropic glutamate receptor analogues can elicit hormone secretion at neuroendocrine/endocrine release sites. Structural constituents of the median eminence, adenohypophysis and neurohypophysis contain elements of glutamatergic transmission, including glutamate receptors and enzymes of the glutamate/glutamine cycle. The synthesis of VGLUT2 exhibits robust up-regulation in response to certain endocrine challenges, indicating that altered glutamatergic signalling may represent an important adaptive mechanism. This review article discusses the newly emerged non-synaptic role of glutamate in neuroendocrine and endocrine communication.
L-谷氨酸是主要的兴奋性神经递质，几乎通过突触机制影响神经内分泌下丘脑的所有神经元。囊泡谷氨酸转运体（VGLUT1 - 3）可将L-谷氨酸选择性地积累到突触小泡中，为在组织学标本中可视化谷氨酸能神经元提供了标志物；内分泌下丘脑中的兴奋性神经元合成VGLUT2亚型。最近的双标记原位杂交研究结果表明，视前区以及下丘脑室旁核、视上核和室周核中的谷氨酸能神经元包括小细胞和大细胞神经分泌神经元，它们将肽类神经激素分泌到血液中以调节内分泌功能。分泌促性腺激素释放激素（GnRH）、促甲状腺激素释放激素（TRH）、促肾上腺皮质激素释放因子（CRF）、生长抑素、催产素和血管加压素的神经元的神经分泌终末含有VGLUT2免疫反应性，提示谷氨酸与促垂体激素肽共同释放。VGLUT2的存在还表明非神经元内分泌细胞（包括垂体前叶的促性腺激素细胞和促甲状腺激素细胞）可分泌谷氨酸。体外研究结果表明，离子型谷氨酸受体类似物可在神经内分泌/内分泌释放部位引发激素分泌。正中隆起、腺垂体和神经垂体的结构成分包含谷氨酸能传递元件，包括谷氨酸受体和谷氨酸/谷氨酰胺循环中的酶。VGLUT2的合成在应对某些内分泌挑战时表现出强烈的上调，表明谷氨酸能信号改变可能代表一种重要的适应性机制。这篇综述文章讨论了谷氨酸在神经内分泌和内分泌通讯中新兴的非突触作用。
