Universidade de Sao Paulo, Instituto de Ciencias Biomedicas, Departamento de Fisiologia e Biofisica, Sao Paulo 05508-000, Brazil.
Edison Biotechnology Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA.
Life Sci. 2020 Oct 15;259:118229. doi: 10.1016/j.lfs.2020.118229. Epub 2020 Aug 8.
Cholinergic neurons are distributed in brain areas containing growth hormone (GH)-responsive cells. We determined if cholinergic neurons are directly responsive to GH and the metabolic consequences of deleting the GH receptor (GHR) specifically in choline acetyltransferase (ChAT)-expressing cells.
Mice received an acute injection of GH to detect neurons co-expressing ChAT and phosphorylated STAT5 (pSTAT5), a well-established marker of GH-responsive cells. For the physiological studies, mice carrying ablation of GHR exclusively in ChAT-expressing cells were produced and possible changes in energy and glucose homeostasis were determined when consuming regular chow or high-fat diet (HFD).
The majority of cholinergic neurons in the arcuate nucleus (60%) and dorsomedial nucleus (84%) of the hypothalamus are directly responsive to GH. Approximately 34% of pre-ganglionic parasympathetic neurons in the dorsal motor nucleus of the vagus also exhibited GH-induced pSTAT5. GH-induced pSTAT5 in these ChAT neurons was absent in GHR ChAT knockout mice. Mice carrying ChAT-specific GHR deletion, either in chow or HFD, did not exhibit significant changes in body weight, body adiposity, lean body mass, food intake, energy expenditure, respiratory quotient, ambulatory activity, serum leptin levels, glucose tolerance, insulin sensitivity and metabolic responses to 2-deoxy-d-glucose. However, GHR deletion in ChAT neurons caused decreased hypothalamic Pomc mRNA levels in HFD mice.
Cholinergic neurons that regulate the metabolism are directly responsive to GH, although GHR signaling in these cells is not required for energy and glucose homeostasis. Thus, the physiological importance of GH action on cholinergic neurons still needs to be identified.
胆碱能神经元分布在含有生长激素（GH）反应细胞的脑区。我们确定了胆碱能神经元是否直接对 GH 有反应，以及特异性删除胆碱乙酰转移酶（ChAT）表达细胞中的 GH 受体（GHR）的代谢后果。
小鼠接受 GH 急性注射，以检测共表达 ChAT 和磷酸化 STAT5（pSTAT5）的神经元，pSTAT5 是 GH 反应细胞的一个公认标志物。为了进行生理研究，产生了仅在 ChAT 表达细胞中删除 GHR 的小鼠，并在消耗常规饲料或高脂肪饮食（HFD）时确定能量和葡萄糖稳态的可能变化。
下丘脑弓状核（60%）和背内侧核（84%）中的大多数胆碱能神经元对 GH 有直接反应。迷走神经背运动核中的大约 34%的节前副交感神经元也表现出 GH 诱导的 pSTAT5。在这些 ChAT 神经元中，GHR ChAT 敲除小鼠中不存在 GH 诱导的 pSTAT5。无论是在常规饲料还是 HFD 中，携带 ChAT 特异性 GHR 缺失的小鼠在体重、体脂肪、瘦体重、食物摄入量、能量消耗、呼吸商、活动量、血清瘦素水平、葡萄糖耐量、胰岛素敏感性和对 2-脱氧-D-葡萄糖的代谢反应方面均无显著变化。然而，ChAT 神经元中的 GHR 缺失导致 HFD 小鼠下丘脑 Pomc mRNA 水平降低。
调节代谢的胆碱能神经元对 GH 有直接反应，尽管这些细胞中的 GHR 信号传导对于能量和葡萄糖稳态不是必需的。因此，GH 对胆碱能神经元作用的生理重要性仍有待确定。
