Distribution of growth hormone-responsive cells in the mouse brain
Distribution of growth hormone-responsive cells in the mouse brain
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DOI：
10.1007/s00429-016-1221-1
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发表时间：
2017-01-01
影响因子：
3.1
通讯作者：
Donato, Jose, Jr.
中科院分区：
文献类型：
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作者：
Furigo, Isadora C.;Metzger, Martin;Donato, Jose, Jr.
生长激素（GH）发挥重要的生物学作用，主要与生长和代谢有关。然而，GH信号在大脑中的作用仍然难以捉摸。为了更好地了解GH在大脑中的功能，我们绘制了GH反应细胞的分布，并确定了参与GH中枢效应的受体。为此目的，小鼠接受急性腹膜内攻击与特定的配体的GH受体（小鼠GH），催乳素受体（催乳素）或两种受体（人GH），和他们的大脑随后进行电化学处理，以检测磷酸化形式的STAT 5（pSTAT 5）。GH诱导pSTAT 5免疫反应的神经元，但不是在许多脑区，包括大脑皮层，脑桥，海马，隔和杏仁核的星形胶质细胞。GH反应神经元的最突出的群体位于下丘脑区域，包括几个视前区，和视上，室旁，视交叉上，室周，弓状，腹内侧，背内侧，结节，后和腹侧乳头体前核。有趣的是，许多脑干结构也表现出GH反应细胞。结合pSTAT 5的免疫组化和GH和催乳素受体的原位杂交的实验显示，人GH诱导pSTAT 5在大多数，但不是所有的，通过催乳素和GH受体的脑区域。此外，雄性和雌性在前脑结构中表现出类似数量的GH反应细胞，这是已知的性二态性。综上所述，我们发现GH反应细胞主要分布在涉及神经植物，情绪/动机和认知功能的脑区。我们的研究结果加深了对大脑中GH信号的理解，并表明中央GH信号可能比以前认识到的更丰富和复杂。
Growth hormone (GH) exerts important biological effects primarily related to growth and metabolism. However, the role of GH signaling in the brain is still elusive. To better understand GH functions in the brain, we mapped the distribution of GH-responsive cells and identified the receptors involved in GH central effects. For this purpose, mice received an acute intraperitoneal challenge with specific ligands of the GH receptor (mouse GH), prolactin receptor (prolactin) or both receptors (human GH), and their brains were subsequently processed immunohistochemically to detect the phosphorylated form of STAT5 (pSTAT5). GH induced pSTAT5 immunoreactivity in neurons, but not in astroglial cells of numerous brain regions, including the cerebral cortex, nucleus accumbens, hippocampus, septum and amygdala. The most prominent populations of GH-responsive neurons were located in hypothalamic areas, including several preoptic divisions, and the supraoptic, paraventricular, suprachiasmatic, periventricular, arcuate, ventromedial, dorsomedial, tuberal, posterior and ventral premammillary nuclei. Interestingly, many brainstem structures also exhibited GH-responsive cells. Experiments combining immunohistochemistry for pSTAT5 and in situ hybridization for GH and prolactin receptors revealed that human GH induced pSTAT5 in most, but not all, brain regions through both prolactin and GH receptors. Additionally, males and females exhibited a similar number of GH-responsive cells in forebrain structures known to be sexually dimorphic. In summary, we found GH-responsive cells primarily distributed in brain regions implicated in neurovegetative, emotional/motivational and cognitive functions. Our findings deepen the understanding of GH signaling in the brain and suggest that central GH signaling is likely more ample and complex than formerly recognized.