Qiu Han, Yang Jin-Kui, Chen Chen
Department of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Endocrinology Department, Tongren Hospital, Capital Medical University, Beijing 100730, China.
Sheng Li Xue Bao. 2017 Oct 25;69(5):541-556.
Growth hormone (GH), as a vital hormone, has to experience a series of processes to fulfill its function including secretion, entering the circulation to reach target tissues (pre-receptor process), binding on the GH receptor (GHR) and triggering signaling inside cells (post-GHR process). Insulin can directly or indirectly influence part of these processes. GH secretion from pituitary somatotropes is regulated by GH-releasing hormone (GHRH) and somatostatin (SS) from hypothalamus. Insulin may exert positive or negative effects on the neurons expressing GHRH and SS and somatotropes under healthy and pathological conditions including obesity and diabetes. Glucose and lipid levels in circulation and dietary habits may influence the effect of insulin on GH secretion. Insulin may also affect GHR sensitivity and the level of insulin-like growth factor 1 (IGF-1), thus influence the level of GH. The GH signaling is also important for GH to play its role. GH signaling involves GHR/JAK2/STATs, GHR/JAK2/SHC/MAPK and GH/insulin receptor substrate (IRS)/PI3K/Akt pathways. These pathways may be shared by insulin, which is the basis for the interaction between insulin and GH, and insulin may attenuate or facilitate the GH signal by influencing molecules in the pathways. Many factors are related to the effect of insulin, among them the most important ones are duration of action and amount of insulin. The tendency of insulin-reduced GH signaling becomes obvious with increased dose and acting time of insulin. The participation of suppressor of cytokine signaling (SOCS), the interaction between JAK2 and IRS, and GHR sensitivity should also be considered when discovering GH signal. The involvement of SS in response to insulin is not clear yet. The details of how GH secretion, level and signaling change in response to time and dose of insulin treatment warrant further studies.
生长激素（GH）作为一种重要的激素，必须经历一系列过程才能发挥其功能，包括分泌、进入循环系统以到达靶组织（受体前过程）、与生长激素受体（GHR）结合并触发细胞内信号传导（GHR后过程）。胰岛素可以直接或间接影响这些过程的一部分。垂体生长激素细胞分泌的GH受下丘脑生长激素释放激素（GHRH）和生长抑素（SS）的调节。在包括肥胖和糖尿病在内的健康和病理状况下，胰岛素可能对表达GHRH和SS的神经元以及生长激素细胞产生正向或负向影响。循环中的葡萄糖和脂质水平以及饮食习惯可能会影响胰岛素对GH分泌的作用。胰岛素还可能影响GHR敏感性和胰岛素样生长因子1（IGF-1）的水平，从而影响GH的水平。GH信号传导对于GH发挥作用也很重要。GH信号传导涉及GHR/JAK2/STATs、GHR/JAK2/SHC/MAPK和GH/胰岛素受体底物（IRS）/PI3K/Akt途径。这些途径可能与胰岛素共享，这是胰岛素与GH相互作用的基础，胰岛素可能通过影响途径中的分子来减弱或促进GH信号。许多因素与胰岛素的作用有关，其中最重要的是作用持续时间和胰岛素剂量。随着胰岛素剂量和作用时间的增加，胰岛素降低GH信号的趋势变得明显。在研究GH信号时，还应考虑细胞因子信号转导抑制因子（SOCS）的参与、JAK2与IRS之间的相互作用以及GHR敏感性。SS在对胰岛素的反应中的作用尚不清楚。胰岛素治疗的时间和剂量如何影响GH分泌、水平和信号传导的具体细节值得进一步研究。
