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.

Sirtuin 1 serum concentration in healthy children - dependence on sex, age, stage of puberty, body weight and diet

“…It is well known that caloric restriction contributes to a state of growth hormone resistance and is associated with a decrease in serum IGF-1 levels, which is a main mediator of growth hormone (GH) action in peripheral tissues. SIRT1 is known to influence the process of intracellular GH signal transduction for IGF-1 synthesis ( 46 ). In situations of fasting or nutrient deficiencies, SIRT1 has been found to decrease the release of IGF-1 from the liver through the STAT5 pathway and enhance resistance to GH by promoting the release of GH from the pituitary gland ( 13 , 47 , 48 ).…”

“…We assessed that SIRT1 serum levels were higher in children that consume more fruits and vegetables (at least 2-3 portions per day). Interestingly, those children were thinner and had lower IGF-1 serum levels, whereas their height was not affected the reduced IGF-1 serum levels may be related to sirtuins ( 46 ), but too many factors affect IGF-1 values to draw conclusions on this topic. Our outcomes are consistent with studies showing that sirtuin 1 may be activated by certain polyphenols, a class of naturally-occurring phytochemicals, which are compounds of some dietary products - fruits and vegetables in particular.…”

Effects of Growth Hormone-Releasing Hormone (GHRH) Plasmid Treatment on the Reproductive Productivity of Sows in Primiparous and Multiparous Sow Breeds

“…This sequence represents an important axis involved in growth regulation, in which GH acts as a stimulator to produce IGF-1 to mediate many of the growth-promoting effects attributed to GH. IGF-1, which is primarily secreted by the liver in response to GH, serves as the main peripheral mediator of GH action [15,16]. This means that IGF-1 plays a crucial role in transmitting the biological signals initiated by GH to various target tissues and organs.…”