Involvement of Sirtuin 1 in the Growth Hormone/Insulin-like Growth Factor 1 Signal Transduction and Its Impact on Growth Processes in Children

Abstract

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.