Department of Endocrinology and Metabolic Diseases, Polish Mother's Memorial Hospital-Research Institute, 93-338 Lodz, Poland.
Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, 93-338 Lodz, Poland.
Int J Mol Sci. 2023 Oct 20;24(20):15406. doi: 10.3390/ijms242015406.
The regulation of growth processes in children depends on the synthesis of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Insulin-like growth factor 1, which is mainly secreted in the liver in response to GH, is the main peripheral mediator of GH action. Newly discovered factors regulating GH secretion and its effects are being studied recently. One of them is sirtuin 1 (SIRT1). This NAD-dependent deacetylase, by modulating the JAK2/STAT pathway, is involved in the transduction of the GH signal in hepatocytes, leading to the synthesis of IGF-1. In addition, it participates in the regulation of the synthesis of GHRH in the hypothalamus and GH in the somatotropic cells. SIRT1 is suggested to be involved in growth plate chondrogenesis and longitudinal bone growth as it has a positive effect on the epiphyseal growth plate. SIRT1 is also implicated in various cellular processes, including metabolism, cell cycle regulation, apoptosis, oxidative stress response, and DNA repair. Thus, its expression varies depending on the different metabolic states. During malnutrition, SIRT1 blocks GH signal transduction in hepatocytes to reduce the IGF-1 secretion and prevent hypoglycemia (i.e., it causes transient GH resistance). In this review, we focused on the influence of SIRT1 on GH signal transduction and the implications that may arise for growth processes in children.
儿童生长过程的调节取决于生长激素 (GH) 和胰岛素样生长因子 1 (IGF-1) 的合成。胰岛素样生长因子 1 主要在肝脏中响应 GH 分泌，是 GH 作用的主要外周介质。最近正在研究新发现的调节 GH 分泌及其作用的因素。其中之一是 Sirtuin 1 (SIRT1)。这种 NAD 依赖性去乙酰化酶通过调节 JAK2/STAT 途径，参与肝细胞中 GH 信号的转导，导致 IGF-1 的合成。此外，它还参与调节下丘脑 GHRH 和生长激素细胞中的 GH 合成。SIRT1 被认为参与生长板软骨生成和长骨生长，因为它对骺板有积极影响。SIRT1 还参与各种细胞过程，包括代谢、细胞周期调节、细胞凋亡、氧化应激反应和 DNA 修复。因此，其表达随不同的代谢状态而变化。在营养不良时，SIRT1 阻断肝细胞中 GH 信号转导，减少 IGF-1 分泌，防止低血糖（即引起短暂性 GH 抵抗）。在这篇综述中，我们重点介绍了 SIRT1 对 GH 信号转导的影响，以及这可能对儿童生长过程产生的影响。
