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Cellular in vivo imaging reveals coordinated regulation of pituitary microcirculation and GH cell network function

机译:细胞体内成像显示垂体微循环和GH细胞网络功能的协调调节

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摘要

Growth hormone (GH) exerts its actions via coordinated pulsatile secretion from a GH cell network into the bloodstream. Practically nothing is known about how the network receives its inputs in vivo and releases hormones into pituitary capillaries to shape GH pulses. Here we have developed in vivo approaches to measure local blood flow, oxygen partial pressure, and cell activity at single-cell resolution in mouse pituitary glands in situ. When secretagogue (GHRH) distribution was modeled with fluorescent markers injected into either the bloodstream or the nearby intercapillary space, a restricted distribution gradient evolved within the pituitary parenchyma. Injection of GHRH led to stimulation of both GH cell network activities and GH secretion, which was temporally associated with increases in blood flow rates and oxygen supply by capillaries, as well as oxygen consumption. Moreover, we observed a time-limiting step for hormone output at the perivascular level; macromolecules injected into the extracellular parenchyma moved rapidly to the perivascular space, but were then cleared more slowly in a size-dependent manner into capillary blood. Our findings suggest that GH pulse generation is not simply a GH cell network response, but is shaped by a tissue microenvironment context involving a functional association between the GH cell network activity and fluid microcirculation.
机译:生长激素(GH)通过从GH细胞网络到血液中的协调性脉动分泌发挥作用。对于网络如何在体内接收其输入并将激素释放到垂体毛细血管中以塑造GH脉冲,人们几乎一无所知。在这里,我们已经开发出了体内方法,可以在小鼠垂体原位以单细胞分辨率测量局部血流量,氧分压和细胞活性。当将促泌素(GHRH)分布用注入血液或附近毛细血管间空间的荧光标记物建模时,垂体实质内会出现限制性分布梯度。注射GHRH会刺激GH细胞网络活动和GH分泌,这与血液流速和毛细血管供氧量增加以及耗氧量在时间上有关。此外,我们在血管周水平观察到了激素输出的限时步骤。注射到细胞外实质中的大分子迅速移至血管周间隙,但随后以取决于大小的方式缓慢清除入毛细血管血液。我们的发现表明,GH脉冲的产生不仅是GH细胞网络的反应,而且还受组织微环境的影响,该环境涉及GH细胞网络活动与流体微循环之间的功能关联。

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