Department of Pediatrics, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
Cells. 2021 Oct 5;10(10):2664. doi: 10.3390/cells10102664.
In mammals, the neuroendocrine system, which includes the communication between the hypothalamus and the pituitary, plays a major role in controlling body growth and cellular metabolism. GH produced from the pituitary somatotroph is considered the master regulator of somatic development and involved, directly and indirectly, in carbohydrate and lipid metabolism via complex, yet well-defined, signaling pathways. GH production from the pituitary gland is primarily regulated by the counter-regulatory effects of the hypothalamic GHRH and SST hormones. The role of IGF-1 feedback regulation in GH production has been demonstrated by pharmacologic interventions and in genetically modified mouse models. In the present review, we discuss the role of IGF-1 in the regulation of the GH-axis as it controls somatic growth and metabolic homeostasis. We present genetically modified mouse models that maintain the integrity of the GH/GHRH-axis with the single exception of IGF-1 receptor (IGF-1R) deficiency in the hypothalamic GHRH neurons and somatotroph that reveals a novel mechanism controlling adipose tissues physiology and energy expenditure.
在哺乳动物中,神经内分泌系统(包括下丘脑和垂体之间的通讯)在控制身体生长和细胞代谢方面发挥着重要作用。垂体生长激素细胞产生的生长激素被认为是躯体发育的主要调节剂,通过复杂但明确的信号通路,直接或间接地参与碳水化合物和脂质代谢。垂体中生长激素的产生主要受下丘脑生长激素释放激素 (GHRH) 和生长抑素 (SST) 激素的反向调节作用调节。通过药理学干预和基因修饰的小鼠模型已经证明了 IGF-1 在 GH 产生中的反馈调节作用。在本综述中,我们讨论了 IGF-1 在调节 GH 轴中的作用,因为它控制着躯体生长和代谢平衡。我们介绍了基因修饰的小鼠模型,这些模型除了下丘脑 GHRH 神经元和生长激素细胞中的 IGF-1 受体 (IGF-1R) 缺陷外,维持 GH/GHRH 轴的完整性,揭示了一种控制脂肪组织生理学和能量消耗的新机制。