**2.6 Growth hormone actions**

Growth hormone (GH) has a wide range of biological effects, many of which are carried out directly by the GH-R and indirectly by IGF-1. The majority, if

#### **Figure 3.**

*The GH/IGF-1 axis and its effects on bone, muscle, and body metabolism. +, stimulation: , inhibition: GHRH, Growth hormone-releasing hormone: cardiovascular system; VO2 Max: maximum oxygen consumption; CVS: cardiovascular system.*

not all, tissues are affected by GH/IGF-1, which has no specific organ as a target as shown in the **Figure 3** [40].

#### *2.6.1 Muscles growth and metabolism*

By increasing protein synthesis and, presumably, limiting protein breakdown by up-regulating the production of Lipoprotein Lipase (LPL), both GH and IGF-1 regulate how quickly muscles break down protein [41, 42]. IGF-1 appears to control the size of human myotubes by promoting protein synthesis, preventing protein breakdown, and causing the reserve cells needed for maximum growth to fuse. Additionally, it has been found that GH causes muscular growth, which is most likely mediated by naturally occurring IGF-1's autocrine and paracrine effects [34]. Additionally, GH has been demonstrated to cause lipid buildup in the muscles, which has been well reported in people with excessive GH (acromegaly), causing skeletal muscle to switch from using glucose to lipids as a substrate [43]. Additionally, there is insufficient evidence—mostly from hypothetical animal studies—to support the idea that growth hormone (GH) may influence the composition of skeletal muscle fibers and cause a switch from glycolytic fast-twitch fibers (type II) to oxidative slow-twitch fibers (type I), which may indicate how GH affects muscle power and strength [44].

#### *2.6.2 Protein metabolism*

Growth hormone (GH) promotes protein synthesis while suppressing proteolysis either directly or through IGF endocrine and paracrines processes, which has an anabolic influence on protein metabolism [45, 46]. The majority of research point to GH's modest anabolic effects, which may include boosting body wide protein production while reducing protein breakdown, as well as reducing muscle-specific amino acid oxidation and degradation [1].

#### *2.6.3 Glucose metabolism*

Growth hormone (GH) is necessary to maintain the metabolism and homeostasis of glucose. While some of these actions are directly induced by IGF-1, others are mostly mediated through its effects that resemble those of insulin (in contrast to those *Carbohydrate Metabolism in Growth Hormone Therapy for Children DOI: http://dx.doi.org/10.5772/intechopen.110778*

of GH) [1]. The GH lipolytic impact appears to be the most important component of GH anti-insulin actions, preventing insulin-stimulated glucose absorption through the oxidation of FFA and consequent inhibition of glycolytic enzymes [47] Additionally, due to its lipolytic properties, GH produced anti-insulin effects that improved hepatic and peripheral insulin sensitivity, increased hepatic glucose production, decreased carbohydrate oxidation, and decreased insulin resistance [48]. Additional mechanisms for the metabolic effects of GH through downregulation of insulin signaling have been proposed, including increased expression of the p85 regulatory subunit of PI3K activity in adipose tissue and enhanced suppressors of cytokine signaling (namely SOCS 1 and 3). [49].

Factors which increase GH release.


### **2.7 Factors that inhibit GH release**

Somatotropin release-inhibitory factor (SRIF) also known as somatostatin which inhibits.

GH release [37].

### **2.8 Obesity**

Obesity is characterized by significantly increased GH synthesis, as evidenced by a nearly pronounced increase in the frequency of GH secretary bursts and half-life duration [55].

### **2.9 Growth hormone physiology and regulation**

Growth hormone (GH, somatotropin) is secreted by somatotrophs which make up about 50 percent of anterior pituitary cells [56]. During these peaks, the plasma

concentration of GH may range from 5 to 35 ng/ml or higher. Peaks may last for five to 30 minutes before resuming baseline levels. A hour or so after the start of sleep, these GH peaks reach their highest and most consistent heights [57]. There are many factors which modulate the production of growth hormone, including stress, nutrition, sleep as stimulator, and free fatty acids which are inhibitor of GH secretion**.** Several molecular isoforms of GH circulate in the plasma. Much of the growth hormone in the circulation is bound to a protein (growth hormone binding protein GHBP) which is derived from the growth hormone receptors [15]. Peptides released by neurosecretory nuclei of the hypothalamus (Growth hormone releasing hormone and somatostatin) into the portal venous blood surrounding the pituitary are the major controllers of GH secretion by the somatotrophs [31]**.**
