IGF-1 and Co. – How to Maximize Growth Factors – Part 1

Dear Readers, Dear PEAK Customers,

In the sports world, everyone has heard of testosterone and its key role in muscle building. The supplement industry is almost desperately trying to find new ways to increase the body’s natural levels of free testosterone, thereby enabling users to achieve faster muscle growth. Growth hormone has certainly been mentioned from time to time as well, since it plays a crucial role in nighttime recovery—including that of the musculature—and, in turn, in the process of protein synthesis.

But how many of you have ever heard of IGF-1 or MGF—and, in this context, nuclei and satellite cells? Among those in the know, they’re now considered the true catalysts for muscle growth. Let’s take a look at this topic today and combine it with a few practical tips to maximize the production of growth factors.

Enjoy!

IGF

IGF is the abbreviation for “insulin-like growth factors,” which are very similar in structure to insulin. They are involved in the growth and differentiation of cells and are produced in both liver cells and other tissues. IGFs enable the body’s cells to communicate with their environment (IGF axis). The entire system consists of membrane receptors (IGF1R, IGF2R), binding proteins (IGFBP 1–6), and several specific enzymes known as IGFBP-associated proteases.

Conclusion

IGFs have their own distribution system and their own receptors, and they do exactly what their name implies: they initiate growth

IGF-1

IGF-1 is the IGF derivative of interest to athletes. It is produced in the liver primarily through stimulation by growth hormone, but also within the muscle cells themselves (here in the subtypes IGF-1Ea, IGF-1Eb, and IGF-1Ec). IGF receptors are present on most cell types. Accordingly, IGF-1 has a significant influence on the entire body. The binding proteins mentioned above transport IGF-1 through the body via the bloodstream. IGF-1 bound to IGFBP-3 appears to support anabolic effects, while IGF-1 bound to IGFBP-1 inhibits them.

IGF-1 exerts its effects on muscle cells by binding to receptors, which trigger a veritable cascade of signals and processes within the cell and, in some cases, initiate an increase in muscle protein synthesis. When IGF-1 binds to its receptor, it also inhibits muscle protein breakdown.  These two properties can be summarized in one word: MUSCLE BUILDING. Studies confirm the significant influence of transgenic overexpression of IGF-1 on regeneration and repair processes. We will discuss the influence of IGF-1 on the formation of satellite cells later.

Note

Of course, IGF-1 also exerts this effect on other types of tissue that express the corresponding receptors; however, this discussion will focus specifically on its effect on skeletal muscle

Conclusion

IGF-1 promotes increased protein synthesis, though not specifically—rather, across a wide variety of tissues. IGF-1 has also been shown to be involved in muscle protein synthesis and to promote tissue regeneration

MGF

Properties and Effects

The IGF-1Ec subtype is better known as MGF (Mechano-Growth Factor). It has already gained a dubious reputation in the doping scene. It is naturally produced in muscles in response to mechanical stress. It is believed that the circulating levels of testosterone and GH in the blood also influence the production of MGF.

MGF acts through a completely different mechanism than the other IGF-1 variants. It activates so-called satellite cells, thereby stimulating the formation of muscle stem cells. When muscle fibers are damaged during training, the satellite cells migrate into the interior of the fibers and begin to mature there. Each of these satellite cells contains a cell nucleus, thereby increasing the number of intramuscular nuclei. Since muscle protein synthesis is initiated by nuclei, the more nuclei present in a muscle fiber, the greater the potential for muscle growth. Understanding the activation and mechanism of action of satellite cells is crucial in this context.

Conclusion

More cell nuclei triggered by exercise and the resulting MGF specifically increase the anabolic potential in the muscle

Interesting

The number of cell nuclei in the muscle also influences the so-called “muscle memory” effect. The more cell nuclei there are in the muscle, the greater the chance of quickly regaining one’s original performance level after prolonged breaks from training. Muscle nuclei do not immediately disappear from the muscle when exercise ceases; rather, they remain there for the time being.

Side Note: Satellite Cells

Satellite Cells

The activity of satellite cells plays a crucial role in muscle regeneration, muscle repair, and muscle growth.

Satellite cells (as mentioned above) constitute the main source of new myonuclei (cell nuclei). They are located on the plasma membrane of muscle fibers. Stress stimuli trigger their activation and a process consisting of proliferation, differentiation, and fusion. Once activated, satellite cells can, as previously mentioned, migrate into the muscle cell and exert various effects there. Activated satellite cells are also referred to as myoblasts.

Conclusion

Satellite cells actively intervene in muscle metabolism

Factors Influencing Satellite Cell Formation

The activation of satellite cells is regulated in our body and is triggered or inhibited by certain factors.

IGF-1

In the case of IGF-1, studies show an effect only when administered via local injection. Systemic administration does not trigger muscle growth resulting from increased satellite cell activation. Supporting this finding, it has been observed that IGF-1 production in muscle occurs independently of circulating growth hormone levels.  Other studies, however, do demonstrate an effect of circulating IGF-1 as well, so no definitive conclusion can yet be drawn here.

MGF, a subtype of IGF-1, is believed to have a faster onset of action but a shorter duration of effect. It is secreted primarily in response to mechanical stimuli. Its effect on satellite cell activation is considered well-established.

Myostatin

Myostatin is also a regulatory factor; however, in this case, it has an inhibitory effect on the activation of satellite cells.

Strength Training

Regarding the influence of strength training, some studies show increased MGF expression in muscle. Even with mild eccentric loads—such as those experienced when running down a hill—there can be an increase in the production of local IGF-1. However, when muscle fibers are damaged by training, the secretion of local IGF-1 is significantly greater.  On the practical side as well, studies combining strength training with nutritional intervention have shown an increase in muscle strength accompanied by elevated IGF-1 expression in skeletal muscle. Hypertrophy was also observed. Plasma concentrations of IGF-1 were not altered by the training; however, there was an average 20% reduction in plasma myostatin levels.

Interesting

The anabolic effect of growth hormone may be attributable to the suppression of myostatin.

Conclusion

The formation of satellite cells is primarily influenced by strength training and the associated increased production of local growth factors. The role of circulating IGF-1 has not yet been clearly established. The formation of satellite cells is inhibited by myostatin

Effect of Activated Satellite Cells

Once activated, some of the satellite cells return to a dormant state and replenish the satellite cell pool. The rest undergo differentiation and fuse with existing muscle fibers, allowing damaged fibers to be repaired. When activated and differentiated satellite cells fuse, new muscle fibers are formed—a process also known as hyperplasia.  Integration into existing muscle fibers triggers an increase in thickness (hypertrophy).

Conclusion

Depending on the circumstances, the activation of satellite cells leads to repair, hypertrophy, or even hyperplasia in the respective muscle

MGF and Doping

MGF has been on the doping list for some time now, as the athletic community is, of course, well aware of the potential of such a growth factor. IGF-1 has, after all, long been a popular substance that is used as a substitute for—or in combination with—growth hormone and stacked with anabolic steroids such as testosterone. The problem with taking such substances, however, is that—as mentioned above—on the one hand, the effects of IGF-1 on the activation of satellite cells following systemic administration have not been conclusively proven. It is considered likely that IGF-1 exerts its muscle-anabolic influence primarily through the described effects on muscle protein synthesis and regeneration. Furthermore, with systemic administration, it is simply not possible to specifically stimulate only the growth of skeletal muscle.

Intramuscular injections of MGF promise a solution here, at least in theory, since the effect can be limited to skeletal muscle—or even to a specific muscle—and the increased formation of cell nuclei has been documented. In principle, the injection achieves what is normally induced by intense strength training; however (as is typical in doping), the amounts used are certainly far higher than those produced physiologically.

Conclusion

At least in theory, the exogenous administration of MGF should enormously increase a muscle’s anabolic capacity, since the limiting factor in muscle growth is always the number of nuclei, and this is precisely the factor being targeted.

Summary

The world of growth factors is a very interesting one. Although today’s article contained a great deal of theory, clear connections to practical applications can still be made. As the name suggests, these factors are primarily concerned with promoting growth.

IGF-1, as one of the growth factor variants from the IGF group, promotes increased muscle protein synthesis, inhibits protein breakdown, and improves the regenerative capacity of the affected tissues. In the case of skeletal muscle, IGF-1 thus promotes muscle growth.

A subtype of IGF-1 produced exclusively in skeletal muscle, known as MGF, promotes muscle growth through a different mechanism by activating so-called satellite cells. Satellite cells influence both the growth and repair processes of muscle fibers by fusing with existing fibers after they have matured; depending on the type of fusion, they repair muscle fibers, promote thickening, or even lead to the growth of new muscle fibers. More muscle fibers mean more muscle cell nuclei, and this is where MGF’s great potential lies, since the number of existing muscle cell nuclei in the muscle fiber can be considered a limiting factor for muscle growth. The extent to which IGF-1 circulating in the blood can also mediate this effect has not yet been clearly established.

In practice, it has been observed that strength training leads to an increase in intramuscular IGF-1 and MGF. Plasma concentrations of IGF-1—induced by strength training—rise only to a limited extent; however, there is a reduction in the plasma levels of myostatin, a protein known to inhibit muscle growth.

In Part 2, I’ll discuss which training methods can be used to maximize the production of growth factors.

Until then, best regards

Yours,

Holger Gugg

www.body-coaches.de

Sources

Satellite Cell Activation During Strength Training – Dt ZSfSM, Vol. 58, No. 1, 2007