Neurohypophyseal Neuregulin 1 Is Derived from the Hypothalamus as a Potential Prolactin Modulator
Neurohypophyseal Neuregulin 1 Is Derived from the Hypothalamus as a Potential Prolactin Modulator
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DOI：
10.1159/000431377
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发表时间：
2015-05
影响因子：
4.1
通讯作者：
Wei-jiang Zhao;Qiong Jiang;J. Mei
中科院分区：
文献类型：
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作者：
Wei-jiang Zhao;Qiong Jiang;J. Mei
虽然神经调节蛋白1 （Nrg1）已经在大鼠下丘脑中被发现，但Nrg1在下丘脑-垂体结构中的定位及其功能尚不清楚，需要进一步阐明。在本研究中，我们发现Nrg1β I-III型在大鼠下丘脑中存在。我们证明Nrg1部分定位于心室周围核的生长抑素阳性细胞。它也与精氨酸加压素共定位于视上核、正中隆起和垂体柄。Nrg1也广泛分布于垂体后叶（PP），包括围绕血管结构和鲱鱼体的突起神经元纤维。Western blotting证实，这些信号主要是由可溶性Nrg1产生的，来源于主要在下丘脑发现的45 kda Nrg1前体。与Nrg1α类似，Nrg1β可增加大鼠垂体RC-4B/C细胞中催乳素（PRL）的表达，并可被Akt抑制剂抑制。此外，Nrg1β在mRNA和蛋白水平上对生长激素的表达无明显影响。总之，我们得出结论，下丘脑Nrg1可能以β形式转运到PP。我们进一步假设Nrg1β可能通过旁分泌机制调节PRL的表达而起作用。
Although neuregulin 1 (Nrg1) has been identified in the rat hypothalamus, the localisation of Nrg1 in the hypothalamus-hypophyseal structure and its functions remain unclear and require further elucidation. In this study, we identified the existence of Nrg1β types I-III in the rat hypothalamus. We demonstrated that Nrg1 was partially localised in somatostatin-positive cells in the periventricular nucleus. It was also co-localised with arginine vasopressin in the supraoptic nucleus, median eminence and pituitary stalk. Nrg1 was also extensively distributed in the posterior pituitary (PP), including the projected neuronal fibres that surround the vascular structure and Herring bodies. Western blotting confirmed that these signals were primarily produced by soluble Nrg1 derived from a 45-kDa Nrg1 precursor mainly identified in the hypothalamus. Similar to Nrg1α, Nrg1β increased the prolactin (PRL) expression in rat pituitary RC-4B/C cells, which can be inhibited by an Akt inhibitor. In addition, Nrg1β had no apparent effect on growth hormone expression at the mRNA or protein levels. Collectively, we conclude that hypothalamic Nrg1 may be transported to the PP as the β form. We further hypothesise that Nrg1β may function via the regulation of PRL expression through a paracrine mechanism.