Missale C, Boroni F, Sigala S, Buriani A, Fabris M, Leon A, Dal Toso R, Spano P
Department of Biomedical Sciences and Biotechnology, University of Brescia, Italy.
Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4240-5. doi: 10.1073/pnas.93.9.4240.
Nerve growth factor (NGF) is well characterized for its neurotrophic actions on peripheral sensory and sympathetic neurons and on central cholinergic neurons of the basal forebrain. Recent evidence, however, has shown high levels of NGF to be present in a variety of biological fluids after inflammatory and autoimmune responses, suggesting that NGF is a mediator of immune interactions. Increased NGF serum levels have been reported in both humans and experimental animal models of psychological and physical stress, thus implicating NGF in neuroendocrine interactions as well. The possible source(s) and the regulatory mechanisms involved in the control of serum NGF levels, however, still remain to be elucidated. We now report the presence of both NGF gene transcripts and protein in the anterior pituitary. Immunofluorescence analysis indicated that hypophysial NGF is selectively localized in mammotroph cells and stored in secretory granules. NGF is cosecreted with prolactin from mammotroph cells by a neurotransmitter-dependent mechanism that can be pharmacologically regulated. Activation of the dopamine D2 receptor subtype, which physiologically controls prolactin release, resulted in a complete inhibition of vasoactive intestinal peptide-stimulated NGF secretion in vitro, whereas the specific D2 antagonist (-)-sulpiride stimulated NGF secretion in vivo, suggesting that the anterior pituitary is a possible source of circulating NGF. Given the increased NGF serum levels in stressful conditions and the newly recognized immunoregulatory function of this protein, NGF, together with prolactin, may thus be envisaged as an immunological alerting signal under neuronal control.
神经生长因子（NGF）因其对周围感觉神经元和交感神经元以及基底前脑的中枢胆碱能神经元的神经营养作用而得到充分表征。然而，最近的证据表明，在炎症和自身免疫反应后，多种生物体液中存在高水平的NGF，这表明NGF是免疫相互作用的介质。在人类和心理及身体应激的实验动物模型中均报告了血清NGF水平升高，因此也表明NGF参与神经内分泌相互作用。然而，血清NGF水平控制中涉及的可能来源和调节机制仍有待阐明。我们现在报告垂体前叶中存在NGF基因转录本和蛋白质。免疫荧光分析表明，垂体NGF选择性地定位于乳腺促性腺细胞中，并储存在分泌颗粒中。NGF通过一种可被药理学调节的神经递质依赖性机制与乳腺促性腺细胞分泌的催乳素共同分泌。多巴胺D2受体亚型的激活在生理上控制催乳素的释放，导致体外血管活性肠肽刺激的NGF分泌完全受到抑制，而特异性D2拮抗剂（-）-舒必利在体内刺激NGF分泌，这表明垂体前叶可能是循环NGF的来源。鉴于应激条件下血清NGF水平升高以及该蛋白新发现的免疫调节功能，NGF与催乳素一起，因此可以被设想为在神经元控制下的免疫警报信号。
