Ojeda S R, Ma Y J
Division of Neuroscience, Oregon Regional Primate Research Center/Oregon Health Sciences University, 505 N.W. 185th Avenue, Beaverton, Oregon 97006, USA.
J Neurobiol. 1999 Sep 15;40(4):528-40. doi: 10.1002/(sici)1097-4695(19990915)40:4<528::aid-neu9>3.0.co;2-v.
It is now clear that astroglial cells actively contribute to both the generation and flow of information within the central nervous system. In the hypothalamus, astrocytes regulate the secretory activity of neuroendocrine neurons. A small subset of these neurons secrete luteinizing hormone-releasing hormone (LHRH), a neuropeptide essential for sexual development and adult reproductive function. Astrocytes stimulate LHRH secretion via cell-cell signaling mechanisms involving growth factors recognized by receptors with either serine/threonine or tyrosine kinase activity. Two members of the epidermal growth factor (EGF) family and their respective tyrosine kinase receptors appear to play key roles in this regulatory process. Transforming growth factor-alpha (TGFalpha) and its distant congeners, the neuregulins (NRGs), are produced in hypothalamic astrocytes. They stimulate LHRH secretion indirectly, via activation of erbB-1/erbB-2 and erbB-4/erbB-2 receptor complexes also located on astrocytes. Activation of these receptors leads to release of prostaglandin E(2) (PGE(2)), which then binds to specific receptors on LHRH neurons to elicit LHRH secretion. Gonadal steroids facilitate this glia-to-neuron communication process by acting at three different steps along the signaling pathway. They (a) increase astrocytic gene expression of at least one of the EGF-related ligands (TGFalpha), (b) increase expression of at least two of the receptors (erbB-4 and erbB-2), and (c) enhance the LHRH response to PGE(2) by up-regulating in LHRH neurons the expression of specific PGE(2) receptor isoforms. Focal overexpression of TGFalpha in either the median eminence or preoptic area of the hypothalamus accelerates puberty. Conversely, blockade of either TGFalpha or NRG hypothalamic actions delays the process. Thus, both TGFalpha and NRGs appear to be physiological components of the central neuroendocrine mechanism controlling the initiation of female puberty. By facilitating growth factor signaling pathways in the hypothalamus, ovarian steroids accelerate the pace and progression of the pubertal process.
现在已经清楚，星形胶质细胞在中枢神经系统内信息的产生和传递过程中发挥着积极作用。在下丘脑，星形胶质细胞调节神经内分泌神经元的分泌活动。这些神经元中的一小部分分泌促黄体生成素释放激素（LHRH），这是一种对性发育和成年生殖功能至关重要的神经肽。星形胶质细胞通过涉及生长因子的细胞间信号传导机制刺激LHRH分泌，这些生长因子由具有丝氨酸/苏氨酸或酪氨酸激酶活性的受体识别。表皮生长因子（EGF）家族的两个成员及其各自的酪氨酸激酶受体似乎在这一调节过程中起关键作用。转化生长因子-α（TGFα）及其远亲神经调节蛋白（NRGs）在下丘脑星形胶质细胞中产生。它们通过激活同样位于星形胶质细胞上的erbB-1/erbB-2和erbB-4/erbB-2受体复合物间接刺激LHRH分泌。这些受体的激活导致前列腺素E2（PGE2）的释放，然后PGE2与LHRH神经元上的特定受体结合，引发LHRH分泌。性腺类固醇通过在信号通路的三个不同步骤发挥作用，促进这种从神经胶质细胞到神经元的通讯过程。它们（a）增加至少一种EGF相关配体（TGFα）的星形胶质细胞基因表达，（b）增加至少两种受体（erbB-4和erbB-2）的表达，以及（c）通过上调LHRH神经元中特定PGE2受体亚型的表达，增强LHRH对PGE2的反应。在下丘脑正中隆起或视前区局部过度表达TGFα会加速青春期。相反，阻断TGFα或NRG在下丘脑的作用会延迟这一过程。因此，TGFα和NRGs似乎都是控制女性青春期启动的中枢神经内分泌机制的生理组成部分。通过促进下丘脑的生长因子信号通路，卵巢类固醇加速青春期进程的速度和进展。
