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Mechano Growth Factor (MGF) and Insulin-Like Growth Factor-1 (IGF-1)

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Mechano Growth Factor (MGF) and Insulin-Like Growth Factor-1 (IGF-1)


we have a few authors on this one

covered in the following

1. What is MGF?
2. What is IGF-1?
3. Theoretical Stacks and Results
4. Member Results MGF
5. Member Results LR3 IGF-1
6. Links to full Cycle Logs
7. Experimental Studies

What is MGF?

Muscle satellite cells are mononuclear cells that remain in a quiescent state until activated when they proliferate and fuse with muscle fibers to donate nuclei, a process necessary for post-embryonic growth, hypertrophy and tissue repair in this post-mitotic tissue. These processes have been associated with expression of the insulin-like growth factor (IGF-I) gene that can undergo alternative splicing to generate different gene products with varying functions. To gain insight into the cellular mechanisms involved in local tissue repair, the time courses of expression of two IGF-I splice variants produced in muscle were determined together with marker genes for satellite cell activation following local muscle damage. Using real-time RT-PCR with specific primers, the mRNA transcripts in rat tibialis anterior muscles were measured at different time intervals following either mechanical damage imposed by electrical stimulation of the stretched muscle or damage caused by injection with bupivacaine. It was found that the autocrine splice variant mechano growth factor (MGF) was rapidly expressed and then declined within a few days following both types of damage. Systemic IGF-IEa was more slowly up regulated and its increase was commensurate with the rate of decline in MGF expression. Satellite cell activation as measured by M-cadherin and one of the muscle regulatory factors MyoD and the sequence of expression suggests that the initial pulse of MGF is responsible for satellite cell activation, as the systemic IGF-IEa mRNA expression peaks after the expression of these markers, including M-cadherin protein. Later splicing of the IGF-I gene away from MGF but towards IGF-IEa seems physiologically appropriate as IGF-IEa is the main source of mature IGF-I for up regulation of protein synthesis required to complete the repair.

What is insulin-like growth factor (IGF-1)?

The insulin-like growth factors (IGFs) are polypeptides with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system (often referred to as the IGF "axis) consists of two cell-surface receptors (IGF1R and IGF2R), two ligands (IGF-I and IGF-II), a family of six high-affinity IGF binding proteins (IGFBP 1-6), as well as associated IGFBP degrading enzymes, referred to collectively as proteases. This system is important for both the regulation of normal physiology, as well as a number of pathological states, including cancer. The IGF axis has been shown to play roles in the promotion of cell proliferation and the inhibition of cell death (apoptosis). IGF-II is thought to be a primary growth factor required for early development while IGF-I expression is seen in later life. Gene knockout studies in mice have confirmed this though other animals are likely to regulate the expression of these genes in distinct ways. While IGF-2 may be primarily fetal in action it is also essential for development and function of organs such as the brain, liver and kidney.

Insulin-like growth factor 1 (IGF-1) is mainly secreted by the liver as a result of stimulation by growth hormone (hGH). Almost every cell in the human body is affected by IGF-1, especially cells in muscle, cartilage, bone, liver, kidney, nerves, skin, and lungs. In addition to the insulin-like effects, IGF-1 can also regulate cell growth and development, especially in nerve cells, as well as cellular DNA synthesis.

IGF-II is secreted by the brain, kidney, pancreas and muscle in mammals. It is more specific in action than IGF-1. In adult humans it is found at 600 times the concentration of insulin.

IGF-1 and IGF-II are regulated by a family of genes known as the IGF-Binding Proteins. These proteins help to modulate IGF action in complex ways that involve both inhibiting IGF action by preventing binding to the IGF-1 receptor as well as promoting IGF action possibly through aiding in delivery to the receptor and increasing IGF half-life. Currently, there are 6 characterized IGF Binding Proteins (IGFBP1-6). There is currently significant data suggesting that IGFBPs play important roles in addition to their ability to regulate IGFs.
Studies of recent interest show that the IGF axis plays an important role in aging. Nematodes, fruit-flies and other organisms have an increased life span when the gene equivalent to the mammalian IGF is knocked out. Clearly the IGF/Insulin axis has an ancient evolutionary origin. Other studies are beginning to uncover the important role the IGFs play in diseases such as cancer and diabetes, showing for instance that IGF-1 stimulates growth of both prostate and breast cancer cells. Researchers are not in complete agreement about the degree of cancer risk that IGF-1 poses.

Further work is required to determine the main receptors used by these growth factors to elicit their effects. Currently the IGF's are known to bind the insulin receptor, IGF-1 receptor, IGF-2 receptor, the insulin-related receptor and possible other receptors. IGF-1 and IGF-2 strongly bind to and activate the IGF-1 receptor, with weaker binding and action occurring through insulin receptors. The IGF-2 receptor only binds IGF-2 and acts as a "clearance receptor" - it activates no intracellular signaling pathways, functioning only as an IGF-2 sequestering agent and preventing IGF-2 signaling.

Theoretical Dosing Protocols / Stacks

Theoretical Dosing Protocols / Stacks / Explanation

Written by LakeMountD

There are many various types of MGF, MGF+IGF-1, IGF-1 stacks that have been attempted and although many of them have been successful, there hasn’t, yet, been a standalone winner. This is due to many factors including availability, price, and little experimental evidence on topics such as down regulation of receptors, antibody production, and suppression of natural hormones/growth factors. There are a lot of people on various boards attempting to “figure out” the scattered scientific data that is spread throughout the internet but it is doing only a small amount of good since most studies conducted on MGF and IGF-1 are done on rats and almost all of the studies done using IGF-1 use the naturally occurring IGF-1. There are a lot of doctors and users who question the safety of exogenous IGF-1 use, however. The prime reason surrounding this questionability is due to the fact that IGF-1 has been shown to increase the growth rate of cancerous tumors. It must be noted, however, IGF-1 does not directly cause cancer, however, if a cancerous cell culture is already forming then IGF-1 can increase the rate of growth through many of the same pathways it increases muscle growth.
In your body IGF-1 is spliced into many different variants that have different anabolic properties. IGF-1Ea and Mechano Growth Factor (MGF or IGF-1Ec) seem to make up the greatest and more important spliced variants of the IGF-1 that is spliced in response to the process of lactosis (lactic acid oxidation caused by the “burn” you feel when lifting weights), which causes muscle damage. The lactic acid is currently thought to be the culprit as well for other irregular spliced variants of IGF-1, such as des 1-3 IGF-1, which is said to be 10 times more potent than that of IGF-1Ea. The most common variant seen in bodybuilding is Long Chain R3 IGF-1 or LR3 IGF-1. This is because LR3 IGF-1 cannot be bound to the IGF-1 Binding Protein 3 (IGF-1 BP3). IGF-1 and IGF-1 BP3 levels are released based off circulating levels of each. As concentrations of IGF-1 in the body rise so do IGF-1 BP3 and as IGF-1 concentrations fall so do IGF-BP3 levels. Recent scientific evidence points out that the reason for IGF-1 BP3 levels rising due to increased levels of IGF-1 is to increase the half-life of circulating IGF-1. Unbound IGF-1 has a half life of around 20 minutes, where as when it’s bound to IGF-1 BP3 the half life is extended to around ~6-10 hours. This is why there is so much excitement surrounding LR3 IGF-1 and now MGF.

Although the exact pathways for muscle growth through the IGF-1 axis aren’t directly known or fully understood, a basic understanding has been established and common mechanisms are currently being discovered. Although the pathways go into a great deal of detail we will be sticking to the main IGF-1 and spliced variant pathways and not into MyoD or M-Cadherin related material, which also play an important role in the grand scheme of things but this could possibly be due to the IGF-1 axis in general, which is why we are only going into detail about it at the moment. It is thought that following muscle damage, circulating levels of IGF-1 are partially spliced towards MGF, which in turn signals muscle damage by proliferating satellite cells(stem cells)/nuclei. As seen in the graph below MGF levels are at their peak 1-2 days following muscle activity and begin to decline rapidly afterwards. IGF-1Ea levels begin to rise at the same time MGF levels begin to fall rapidly, around day 4. MGF proliferates cells in their mononucleated states (muscle stem cells), which is an important piece of the recovery puzzle since without these new stem cells there can be no new growth. This is seen in people with muscular dystrophy and although their bodies still produce IGF-1, their muscles do not exhibit MGF expression, showing the importance for MGF in recovering damaged muscles. Although MGF does proliferate these new stem cells as well as increase protein synthesis to a slight degree, MGF also inhibits differentiation in muscle cells (differentiation can be defined as: myoblast alignment, elongation, and fusion into multinucleate myotubes, together with the induction of regulatory and structural muscle-specific genes rises around the same time. IGF-1Ea completes the repairs by drastically increasing protein synthesis and differentiating these newly brought stem cells. Another possibility for IGF-1 is muscle hyperplasia. Although hypertrophy, which is seen with AAS usage and normal training, is the enlargement of the actual muscle, hyperplasia is the actual increase in muscle myotubes. Hyperplasia will not be discussed in detail in this manual until it is more fully understood given scientific evidence based off of studies conducted by trusted scientists. Although many have stated that hyperplasia is impossible without exogenous use of IGF-1, this is a somewhat false statement; a better statement would be that IGF-1 induced hyperplasia occurs at a VERY slow rate naturally since at any given time less than 1% of all IGF-1 circulating in the blood is unbound from IGF-1 BP3. One must also know that despite IGF-1’s effects on muscle hyperplasia and the increased rate at which it occurs when using exogenous LR3 IGF-1, the overall results that are seen can often be seen at their greatest a fair amount of time after using LR3. This occurs due to the fact that newly made myotubes are not matured instantly during the process of hyperplasia. Instead, these cells must go through the process of hypertrophy before they mature and become enlarged, another exciting reason to use a combination of MGF and LR3 IGF-1. This is the process of body recomposition that people talk so much about on bodybuilding forums throughout the internet. You can technically work around your genetic limit and move past it. It must also be noted that in recent studies caloric restriction had no significant effect on MGF, IGF-1, or IGF-1Ea (systemic, liver form of IGF-1) receptor count, making the possibility for exogenous LR3 IGF-1/MGF as potent, muscle sparing cutter, a great idea.
Now that all of this basic knowledge of IGF-1 and MGF has been given to you, we can attempt to set up cycles based off of it. Actual dosing protocols for these growth factors (not including hGH) is quite difficult because unlike hormones such as T3 that can be tested for and, therefore, dosed according to circulating levels, it is almost impossible to detect how much MGF is released following muscle loading or how much of a spliced variant such as LR3 IGF-1 needs to be dosed to prevent antibody production or down regulation of receptors, since LR3 IGF-1 doesn’t occur naturally in the body (except under freak splicing caused by lactic acid, which is a rare occurrence) and all studies done are based off of the naturally occurring IGF-1. This leads us into human testing based off abstract results by brave guinea pigs looking for that extra edge. Although great results have been seen dosing LR3 IGF-1 at 60-120mcg daily following intense exercise, results begin to taper off after around 4 weeks and down regulation of IGF-1 receptors and IGF-1 antibody production is currently thought to be the culprit. This leads one to believe that following a lower dosage scheme for a longer amount of time would be the way to go. It seems that not many people are willing to attempt a cycle consisting of 10-20mcg daily of LR3 IGF-1 due to the cost of LR3 IGF-1 being anywhere from $115-$200 depending on the source and many feel that a lower dosage would be a waste since “instant” results are not seen. MGF has been shown exhibit its effects even while the IGF-1 receptor was blocked in many studies, proving that MGF works through other various pathways and does not attach to the IGF-1R, making it invulnerable to downregulation. Since hGH has been said to contribute most of its effects thanks to increased IGF-1 production, the level of IGF-1 produced by administrating exogenous hGH has to be extremely small compared to the amounts currently being injected, which is probably why exogenous hGH results last indefinitely, as seen by many people who use it year round. These small amounts released are not enough to cause downregulation or antibody production. This would be one reason for lower dosage of IGF-1 to be used. An alternative camp says shorter cycles of higher dosages are more important since they want to rapidly increase the rate of muscle hypertrophy/hyperplasia before side effects and blunting effects are seen.

MGF dosages have also been widely debated. Although dosages are currently ranging from 20-100+ mcg injected bilaterally following intense exercises, you have to once again think to yourself how much MGF this is when compared to the amount your body is naturally producing. If only less than 1% of IGF-1 is circulating through your blood in the unbound state, and MGF is produced from splicing IGF-1 into MGF, than the amount relative to the 100mcg that people are currently administering is an extremely massive quantity. However, before you consider this a waste to inject this amount of exogenous MGF, it might be a good idea to use these concentrations after all, since the muscle could ultimately be extremely over trained, hitting much more of the muscle and causing greater damage to more muscle fibers and still be able to recover in time for the next workout due increased nuclei/satellite cell production. Add LR3 IGF-1 to the mix and you have a potent combination of recover and repair that your body uses itself after intense exercise. Since the cost of MGF is currently ~$100/mg and the effects, unlike LR3 IGF-1, are localized, one should limit its use to 1 or maybe 2 lagging body parts per cycle to get the max effect. In the figures below you will see how your body responds in a worked and non-worked muscle in response to release of MGF. In the study a rabbit was subjected to stimulation of his left leg while the right leg was held relaxed. MGF increased drastically on the left side while very minimally in the right side, showing that MGF is indeed localized. After review of all the evidence and scientific data it would seem logical to set up a dosage scheme such as the following although this has not be experimentally verified yet and there could be potentially better ways of dosing and cycling.

MGF + LR3 IGF-1 Dosage Scheme (following intense loading of lagging muscle group)

Day 1
Pre Workout (~6 hours)- 20-50mcg total MGF
Post Workout- 20-50mcg x 2 MGF (left and right sides of lagging muscle) following workout

Day 2
Morning- 20mcg LR3 IGF-1
20-50mcg x 2 in lagging muscle group MGF
Afternoon-20-50mcg x 2 in lagging muscle group MGF
Late afternoon (at least 10 hours after first injection optimally)- 20mcg LR3 IGF-1

Day 3
Morning- 20mcg LR3 IGF-1
Late Afternoon- 20mcg LR3 IGF-1

Day 4
Morning- 20mcg LR3 IGF-1
Late Afternoon- 20mcg

Day 5
Morning- 20mcg LR3 IGF-1
Late Afternoon- 20mcg

This is a great way to kick start a lagging muscle group with high dosages of potent growth factors. This dosage scheme follows the graph below, which is the body’s natural way of repairing muscle, just with much higher dosages. This dosage scheme also seems logical to prevent too much down regulation of receptors. Although there is no scientific data that backs up administering MGF pre workout; results from various people indicate that better gains and quicker recovery times were observed, possibly due MGF’s ability to proliferate satellite cells, but since this takes time, the cells could be available directly after you are done with your workout when given a pre workout injection of it. It must also be noted that overtraining the lagging muscle group could possibly lead to increased muscle hypertrophy when using exogenous LR3 IGF-1 and MGF in combination. An experiment conducted by Dr. Goldspink was created to experiment with the ability of the IGF-1 axis to repair damaged muscle. Four groups were created: a sham group, a normal group, a consistently stretched/stimulated group (s/s), and a bicupivaine injected group (bup). The results were extremely interesting. While the control groups saw basically no change in their muscle mass, the s/s group had ~12% less mass after s/s, whilst the bup group showed a 1/3 reduction of their weight 4 days following the bup injection. They then graphed the amounts of IGF-1Ea and MGF present in their muscles following muscle damage (graph below). They found that 14 days following s/s the rats of this group saw no change in weight (probably due to the fact the diets aren’t on a high calorie, high protein diet like most bodybuilders) while the rats injected with bup saw a 10% increase in weight, although it took 24 days total for this to occur. This shows that since bup affected more muscle fibers it allowed more of the MGF induced satellite cells/nuclei to fuse to the damaged cells and to be activated and also allowed greater recovery and use of circulating amino acids caused by the increase in IGF-1Ea a few days following. As seen however, those injected with bup took twice as long to recover. This would lead one to believe that overtraining the specific muscle group or basically getting more of a burn and more of a soreness the next day would lead to increased hypertrophy in a hypocaloric diet when injecting exogenous LR3 IGF-1 and MGF, although exact dosages are not yet clear. There are many possible outcomes. One is the fact that vastly increased amounts of MGF and LR3 IGF-1 present from exogenous use will be sufficient enough to repair the muscle in a much shorter amount of time than your body would take to use its natural sources. The second outcome is that dosages will need to be significantly ramped up or taken for longer periods of time for proper recover to occur, although I feel either the first or a mixture of the two will probably suffice. I will soon be experimenting with this overtraining and experimentation following my personal MGF + LR3 IGF-1 use and results will be posted shortly thereafter.

(written by xtraflossy)
MGF Solo dosing:
There seem to be many schools of thought. Post workout is generally agreed on, but include a number of variations. The amount of Mechano Growth Factor administered differs greatly (from 20mcg – 100+mcg). While ultimately one dose doesn’t fit everyone’s needs, excessive amounts of MGF (without exogenous IGF-1 supplementation) have not yet proven to provide better results.
Below are some of the tried dosing protocols and their explanations. If possible, links have been provided to Logs of that particular dosing schedule and/or discussion on that particular method.

Post workout Only:

Description: Simply injecting Mechano-Growth Factor into the worked muscle after training. Your body expresses MGF in response to mechanical overload (micro trauma to muscle tissue). MGF is responsible for repair (by means of activating satellite cells to begin to donate (replicate) nuclei. These nuclei are then used to repair the damaged tissue. MGF is also responsible for muscle adaptation (hypertrophy). The reasoning behind this method is simple. Greater MGF expression leads to a greater response in muscle adaptation because the body thinks more damage has been caused then there actually is.


Post Workout +
(plus X days after)
Description: Similar to Post workout only, with MGF administration continued for a number of days afterwards. The reasoning here is supported by the bodies natural ability to express MGF longer then one day post workout. Increasing the amount of MGF in the trained muscle beyond the initial post workout injection should elicit a greater response for a longer time. It is important to note that at this time it is not known how long MGF (the Peptide) survives or remains active once injected. The length of time one would administer MGF post workout depends on many things unique to the user (recovery time, usage costs, diet…)


(x hours pre w/o, immediately after workout and following morning)
Description: This theory differs in regards to the above mentioned. MGF is administered hours BEFORE working the muscle. A post workout injection is also administered, and one the following morning (or about 12 hours after the post workout injection). The amount of MGF is not increased, rather user would split the dose used, using half a number of hours before exercise of the muscle, and the other half is to be used post workout. The 3rd dose would be a normal “full” dose 12 hours later. Thus method uses the same amount of peptide as the Post workout + protocol does (assuming MGF is administered the day after training and then ceased).
The reasoning behind this protocol is believed to be that the pre-workout injection a few hours before training activates the satellite cells to donate their nuclei. Since there is not yet muscle damage, the donated nuclei will increase in number. This increase before muscle trauma gives a “head start” in the repair process via having already pre-made, available cells the second damage occurs to the muscle, speeding recovery (and/or increased training ability).

Log: Mechano Growth Factor !! Post #1

Member Results for LR3 IGF-1 (abstract)
done at anabolicminds.com

Members were asked:
1. How many cycles have you done?
JBlaze: Only one so far. Did it during PCT. My next cycle will be during an AAS cycle.
ManBeast: One cycle of IGF1-LR3 during PCT.
Nuteboy: How many cycles have you done? One cycle.
Longdog: 2 cycles of IGF1-LR3. 1 off cycle & 1 during PCT.
BryanFury: One stand alone cycle
er700: 1 cycle along with test and eq
IntResearch: 2
Raprazant: 1

2. How long were you on igf-1?
JBlaze: 21 days, at this point i noticed the gains stopped coming, so i decided to come off.
ManBeast: 28 days.
Nuteboy: Five weeks.
Longdog: 4 weeks & 3 weeks
BryanFury: 22 days
er700: 25 days
IntResearch: 1 month
Raprazant: 30 days

3. How many mcg did you use?
JBlaze: I used 40mcg in the beginning and bumped it up to 60 mcg. At 60mcg i noticed better results, so my next cycle will consist of 60mcg throughout.
ManBeast: 30mcg ED
Nuteboy: First three days I used 200mcg per day but once I was told how to calculate mcg's I'd do 40mcg per day.
Longdog: 30mcg ED
BryanFury: 40mcg ED
er700: 40
IntResearch: 40/75
Raprazant: 100 mcg/day with one day off every 6 days

4. How many times a day did you shoot?
JBlaze: Once a day after my workout, and first thing in the morning on non-workout days.
ManBeast: Once a day, sometime after my workout.
Nuteboy:.Once per day. Usually after my workout.
Longdog: Once a day, IM bilaterally into muscle worked, immediately after training.
BryanFury: Once a day, pre-workout
er700: once a day after workouts
IntResearch: Once
Raprazant: once, after workouts

5. How much fat loss and muscle gain was there overall?
JBlaze: Gained 4lbs of muscle and lost 1.5lbs of fat. Keep in mind this cycle was during PCT.
ManBeast: Lost some fat and gained definition during PCT.
Nuteboy: How much fat loss and muscle gain was there overall? Difficult to figure how much fat lost but I am leaner this offseason than last year.
The first four days I gained 4 to 5lbs. Overall I'd say 8lbs of solid muscle.
Longdog: Once a day, IM bilaterally into muscle worked, immediately after training.
BryanFury: Lost some fat, body comp. changed overall. Gained roughly 5lbs.
er700: ~2 pounds of muscle and loss ~ 3 pounds of fat. At the time I was getting ready for a powerlifting comp. and was eating very clean to get my bwt. down to 220, I normally weigh over 240.
IntResearch: 2 loss, 5 gain
Raprazant: 6 lbs. of fat loss, 4 lbs of muscle gain give or take a lb of each

6. How likely are you to use it again?
JBlaze: I already have 2 bottles sitting here, and i got 2 more on the way. I'll never do PCT w/o this again.
ManBeast: Very likely.
Nuteboy: Very. I will use it again "offseason" but will include insulin.
Longdog: Will definitely use it again, but will use 40mcg or more.
BryanFury: Plan on a second 4 weeks after the last ended.
er700: Definitely, getting ready to use it along with my PCT
IntResearch: very likely, only dislike was getting sleepy after injecting
Raprazant: very likely but with hgh

7. What strength gains did you see?
JBlaze: Hardly any at all, but then i do extremely slow concentrated movements, i rarely go up in weight.
ManBeast: I don't attribute the strength gains made to this, more to the low-rep lifting scheme I was using.
Nuteboy: Not much in the strength gains as I normally lift heavy.
I would not say IGF made me stronger but made me look FULL as hell.
Longdog: No strength gains. Look elsewhere if that's what you want, this is not an androgen.
BryanFury: Strength was placebo effect I think. Muscles did get more full with increased vascularity.

8. Finally did you use AAS with the IGF -1?
JBlaze: This cycle it was igf-1 alone, but my next cycle i will be using it week 5-9 of my AAS cycle. Then my 3rd and final cycle for a while will be during my last 2 weeks on AAS, and 2 weeks into PCT.
ManBeast: Nope
Nuteboy: Yes. I used Test and Deca.
Longdog: No, but I will use it on a cycle next time.
BryanFury: No


-Muscle satellite (stem) cell activation during local tissue injury and repair
-Growth factors and muscle ageing.
-Are the metabolic effects of GH and IGF-I separable?
-IGF-I/IGFBP-3 ameliorates alterations in protein synthesis, eIF4E availability, and myostatin in alcohol-fed rats.
-Impairment of IGF-I gene splicing and MGF expression associated with muscle wasting.
-A strong neuroprotective effect of the autonomous C-terminal peptide of IGF-1 Ec (MGF) in brain ischemia.
-Mechanical signals, IGF-I gene splicing, and muscle adaptation.
-Impact of resistance loading on myostatin expression and cell cycle regulation in young and older men and women.
-Age-related loss of skeletal muscle function; impairment of gene expression.
-Mechanical signals and IGF-I gene splicing in vitro in relation to development of skeletal muscle.
-Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise.

Muscle satellite (stem) cell activation during local tissue injury and repairMaria Hill, A. Wernig and G. Goldspink

In post-mitotic tissues, damaged cells are not replaced by new cells and hence effective local tissue repair mechanisms are required. In skeletal muscle, which is a syncytium, additional nuclei are obtained from muscle satellite (stem) cells that multiply and then fuse with the damaged fibers. Although insulin-like growth factor-I (IGF-I) had been previously implicated, it is now clear that muscle expresses at least two splice variants of the IGF-I gene: a mechanosensitive, autocrine, growth factor (MGF) and one that is similar to the liver type (IGF-IEa). To investigate this activation mechanism, local damage was induced by stretch combined with electrical stimulation or injection of bupivacaine in the rat anterior tibialis muscle and the time course of regeneration followed morphologically. Satellite cell activation was studied by the distribution and levels of expression of M-cadherin (M-cad) and related to the expression of the two forms of IGF-I. It was found that the following local damage MGF expression preceded that of M-cad whereas IGF-IEa peaked later than M-cad. The evidence suggests therefore that an initial pulse of MGF expression following damage is what activates the satellite cells and that this is followed by the later expression of IGF-IEa to maintain protein synthesis to complete the repair.

Growth factors and muscle ageing
Goldspink G, Harridge SD.
Aximygen/UCL Biomedica, Division of Surgery, Royal Free and University College Medical School, The Archway Campus, 2-10 Highgate Hill, London N19 5LW, UK. goldspink@rfc.ucl.ac.uk

Loss of muscle mass (sarcopenia) is one of the main problems associated with ageing as it has major health care as well as socioeconomic implications. The growth hormone (GH)/IGF-I axis is regarded as an important regulator of muscle mass. However, it is now appreciated that other tissues in addition to the liver expressed IGF-I and that there are local as well as systemic forms of IGF-I which have different functions. At least two different kinds of IGF-I that are expressed by skeletal muscle are derived from the IGF-I gene by alternative splicing, one of which is expressed in response to physical activity which has now been called 'mechano growth factor' (MGF). The other is similar to the systemic or liver type (IGF-IEa) and is important as the provider of mature IGF-I required for up regulating protein synthesis. MGF differs from systemic IGF-IEa in that it has a different peptide sequence which is responsible for replenishing the satellite (stem) cells in skeletal muscle. The ability to produce MGF declines with age, and this is commensurate with the decline in circulating GH levels. GH treatment up regulates the level of IGF-I gene expression in older people and when combined with resistance exercise more is spliced towards MGF and hence should improve the ability of muscle to respond to physical activity. The possibility of ameliorating sarcopenia using MGF is discussed.

Are the metabolic effects of GH and IGF-I separable?
Mauras N, Haymond MW.
Division of Endocrinology, The Department of Pediatrics at the Nemours Children's Clinic, 807 Children's Way, Jacksonville, FL 32207, USA. nmauras@nemours.org

IGF-I mediates some, but not all of the metabolic actions of GH and it has both GH-like and insulin-like actions in vivo. GH and IGF-I both have a net anabolic effect in man enhancing whole body protein synthesis over a period of weeks and perhaps months. Both hormones favorably improve body composition in GH deficient subjects with an increase in lean body mass and decreased adiposity. This is also observed when IGF-I is given to patients with GH-receptor mutations. These compounds, however, have divergent effects on carbohydrate metabolism. A potent glucose lowering effect is typically observed after IGF-I administration, with improved insulin sensitivity with marked lowering of circulating insulin concentrations, whereas GH therapy is associated with mild compensatory hyperinsulinemia, a reflection of relative insulin resistance. The latter observation makes IGF-I a potentially more convenient anabolic agent to use in conditions where carbohydrate metabolism is more likely to be impaired. GH increases lipolysis as a direct effect of GH on the adipocyte, as well as lipid oxidation by increasing substrate availability. However IGF-I increases lipid oxidation only when given chronically, most likely as a result of chronic insulinopenia. These compounds have been tried in a variety of catabolic conditions in man and both hormones have been effective in reducing the protein wasting effects of glucocorticosteroids and mitigate some of the catabolic effects of severe hypogonadism in males. A comparison of these and other effects of these hormones is provided in this brief review. Subsequent studies are still needed to fully elucidate the safety and efficacy of IGF-I for use in humans.

IGF-I/IGFBP-3 ameliorates alterations in protein synthesis, eIF4E availability, and myostatin in alcohol-fed rats.Lang CH, Frost RA, Svanberg E, Vary TC.
Department of Cellular & Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. clang@psu.edu

Chronic alcohol consumption decreases the concentration of the anabolic hormone IGF-I, and this change is associated with impaired muscle protein synthesis. The present study evaluated the ability of IGF-I complexed with IGF-binding protein (IGFBP)-3 to modulate the alcohol-induced inhibition of muscle protein synthesis in gastrocnemius. After 16 wk on an alcohol-containing diet, either the IGF-I/IGFBP-3 binary complex (BC) or saline was injected two times daily for three consecutive days. After the final injection of BC (3 h), plasma IGF-I concentrations were elevated in alcohol-fed rats to values not different from those of similarly treated control animals. Alcohol feeding decreased the basal rate of muscle protein synthesis by limiting translational efficiency. BC treatment of alcohol-fed rats increased protein synthesis back to basal control values, but the rate remained lower than that of BC-injected control rats. The BC partially reversed the alcohol-induced decrease in the binding of eukaryotic initiation factor (eIF)4E with eIF4G. This change was associated with reversal of the alcohol-induced dephosphorylation of eIF4G but was independent of changes in the phosphorylation of either 4E-BP1 or eIF4E. However, BC reversed the alcohol-induced increase in IGFBP-1 and muscle myostatin, known negative regulators of IGF-I action and muscle mass. Hence, exogenous IGF-I, administered as part of a BC to increase its circulating half-life, can in part reverse the decreased protein synthesis observed in muscle from chronic alcohol-fed rats by stimulating selected components of translation initiation. The data support the role of IGF-I as a mediator of chronic alcohol myopathy in rats.

Impairment of IGF-I gene splicing and MGF expression associated with muscle wasting.Goldspink G.
Department of Surgery, Royal Free and University College Medical School, London, UK. g.goldspink@medsch.ucl.ac.uk

The characterisation of a local tissue repair factor (mechano growth factor, MGF) that is produced by exercised and/or damaged muscle by differential splicing of the IGF-I gene provides understanding of how muscle is maintained in the young normal individual. Mechano growth factor, or MGF, is different to the systemic IGF-I as it has an insert of 49 base pairs in exon 5 that introduces a reading frame shift resulting in a C terminal peptide with unique properties. Muscle is a post-mitotic tissue and as cell replacement is not a means of tissue repair there has to be an efficient local repair mechanism otherwise the damaged cells undergo cell death. The extra nuclei for muscle repair and hypertrophy are provided by the muscle satellite (stem) cells. The pool of these stem cells is apparently replenished by the action of MGF, which is produced as a pulse following a mechanical challenge. Unfortunately, the production of MGF is deficient in certain diseases such as in the muscular dystrophies in which the mechanotransduction mechanism, which may involve the dystrophin complex, is defective. In elderly muscles, decreased levels of growth hormone apparently mean that there is less primary RNA transcript of the IGF-I gene to be spliced towards MGF. Consequently, there is an increasing inability to maintain muscle mass during ageing. Delivery of MGF and cDNA or peptide produces marked increases in the strength of normal as well as diseased muscle and, therefore, MGF has considerable potential as a generic means of treating muscle cachexia.

A strong neuroprotective effect of the autonomous C-terminal peptide of IGF-1 Ec (MGF) in brain ischemia.
Dluzniewska J, Sarnowska A, Beresewicz M, Johnson I, Srai SK, Ramesh B, Goldspink G, Gorecki DC, Zablocka B.
Molecular Biology Unit, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

The ischemic stroke is the third leading cause of death in developed countries. The C-terminal peptide of mechano-growth factor (MGF), an alternatively spliced variant of insulin-like growth factor 1 (IGF-1), was found to function independently from the rest of the molecule and showed a neuroprotective effect in vivo and in vitro. In vivo, in a gerbil model of transient brain ischemia, treatment with the synthetic MGF C-terminal peptide provided very significant protection to the vulnerable neurons. In the same model, ischemia evoked increased expression of endogenous MGF in the ischemia-resistant hippocampal neurons, suggesting that the endogenous MGF might have an important neuroprotective function. In an in vitro organotypic hippocampal culture model of neurodegeneration, the synthetic peptide was as potent as the full-length IGF-1 while its effect lasted significantly longer than that of recombinant IGF-1. While two peptides showed an additive effect, the neuroprotective action of the C-terminal MGF was independent from the IGF-1 receptor, indicating a new mode of action for this molecule. Although MGF is known for its regenerative capability in skeletal muscle, our findings demonstrate for the first time a neuroprotective role against ischemia for this specific IGF-1 isoform. Therefore, the C-terminal MGF peptide has a potential to be developed into a therapeutic modality for the prevention of neuronal damage.

Mechanical signals, IGF-I gene splicing, and muscle adaptationGoldspink G.
Basic Division of Basic Medical Sciences and Department of Surgery, Royal Free and University College Medical School, London, UK. goldspink@medsch.ucl.ac.uk

Combining physiological and molecular biology methods made it possible to identify and characterize a local muscle growth/repair factor (MGF). Following resistance exercise, MGF "kick starts" muscle hypertrophy and is important in local tissue repair. Loss of muscle mass in old age and certain diseases is associated with an impaired ability to express MGF.

Impact of resistance loading on myostatin expression and cell cycle regulation in young and older men and women.Kim JS, Cross JM, Bamman MM.
UAB Dept. of Physiology and Biophysics, Muscle Research Laboratory, GRECC/11G, Veterans Affairs Medical Center, 1530 3rd Ave. South, Birmingham, AL 35294-0001, USA.

Myostatin inhibits myoblast proliferation and differentiation in developing muscle. Mounting evidence suggests that myostatin also plays a limiting role in growth/repair/regeneration of differentiated adult muscle by inhibiting satellite cell activation. We tested the hypothesis that myostatin mRNA expression would decrease after resistance loading (RL) with a blunted response in older (O) females (F) who have shown minimal hypertrophy [vs. males (M)] after long-term RL. As myostatin is thought to modulate cell cycle activity, we also studied the response of gene transcripts key to stimulation (cyclin B1 and D1) and inhibition (p21cip and p27kip) of the cell cycle, along with the muscle-specific load-sensitive mitogen mechano-growth factor (MGF). Twenty young (Y; 20-35 yr, 10 YF, 10 YM) and 18 O (60-75 yr, 9 OF, 9 OM) consented to vastus lateralis biopsy before and 24 h after a bout of RL (3 sets x 8-12 repetitions to volitional fatigue of squat, leg press, knee extension). Gene expression levels were determined by relative RT-PCR with 18S as an internal standard and analyzed by age x gender x load repeated-measures ANOVA. A load effect was found for four transcripts (P < 0.005) including myostatin, cyclin D1, p27kip, and MGF as mRNA levels decreased for myostatin (-44%) and p27kip (-16%) and increased for cyclin D1 (34%) and MGF (49%). For myostatin, age x load and gender x load interactions (P < 0.05) were driven by a lack of change in OF, while marked declines were noted in YM (-56%), YF (-48%), and OM (-40%). Higher cyclin D1 levels in OF led to a main age effect (36%, O > Y) and an age x gender interaction (66%, OF > YF vs. 10%, OM > YM; P < 0.05). An age x gender x load interaction (P < 0.05) for cyclin D1 resulted from a 48% increase in OF. Post hoc testing within groups revealed a significant increase in MGF after RL in YM only (91%, P < 0.05). Higher levels of cyclin B1 in O (27%, O > Y) led to a main age effect (P < 0.05). An age x load interaction for cyclin B1 (P < 0.05) was driven by a 26% increase in Y with no change in O after RL. No age or gender differences, or load-mediated changes, were detected in levels of p21cip mRNA expression. These data clearly demonstrate that RL downregulates myostatin expression and alters genes key to cell cycle progression. However, failure to reduce myostatin expression may play a role in limiting RL-induced hypertrophy in OF

Age-related loss of skeletal muscle function; impairment of gene expression.
Goldspink G.
Division of Surgery and Reconstructive Medicine, Royal Free and University College Medical School, Royal Free Campus, London, UK. goldspink@rfc.ucl.ac.uk

Mechano Growth Factor (MGF) is derived from the insulin-like growth factor (IGF-I) but its sequence differs from the systemic IGF-I produced by the liver. MGF is expressed by mechanically overloaded muscle and is involved in tissue repair and adaptation. It is expressed as a pulse following muscle damage and involved in the activation of muscle satellite (stem) cells. These donate nuclei to the muscle fibers that are required for repair and for the hypertrophy processes which may have similar regulatory mechanisms. Muscles in the elderly are unable to upregulate MGF in response to exercise. This is also true in certain diseases and this helps to explain muscle loss in those conditions. There is evidence that MGF is a local tissue repair factor as well as a growth factor and that it has an important role in damage limitation and inducing repair in other post-mitotic tissues. As there is no cell replacement in these tissues there has to be an effective local cellular repair mechanism. With advancing years this seems to become deficient and there is an increased chance that the damaged cells will undergo cell death leading to progressive loss of tissue function.

Mechanical signals and IGF-I gene splicing in vitro in relation to development of skeletal muscleCheema U, Brown R, Mudera V, Yang SY, McGrouther G, Goldspink G.
Institute of Orthopaedics and Musculo-skeletal Science, University College London, Middlecoïtus, United Kingdom.

It has been shown that the insulin-like growth factor (IGF-I) gene is spliced in response to mechanical signals producing forms of IGF-I which have different actions. In order to study how mechanical signals influence this gene splicing in developing muscle, C2C12 cells were grown in three-dimensional (3D) culture and subjected to different regimens of mechanical strain. IGF-IEa which initiates the fusion of myoblasts to form myotubes was found to be constitutively expressed in myoblasts and myotubes (held under endogenous tension) and its expression up regulated by a single ramp stretch of 1-h duration but reduced by repeated cyclical stretch. In contrast, mechano growth factor (MGF), which is involved in the proliferation of mononucleated myoblasts that are required for secondary myotube formation and to establish the muscle satellite (stem) cell pool, showed no significant constitutive expression in static cultures, but was up regulated by a single ramp stretch and by cycling loading. The latter types of force simulate those generated in myoblasts by the first contractions of myotubes. These data indicate the importance of seeking to understand the physiological signals that determine the ratios of splice variants of some growth factor/tissue factor genes in the early stages of development of skeletal muscle. 2005 Wiley-Liss, Inc.

Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise.Hameed M, Orrell RW, Cobbold M, Goldspink G, Harridge SD.
Department of Physiology, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK.

The mRNA expression of two splice variants of the insulin-like growth factor-I (IGF-I) gene, IGF-IEa and mechano growth factor (MGF), were studied in human skeletal muscle. Subjects (eight young, aged 25-36 years, and seven elderly, aged 70-82 years) completed 10 sets of six repetitions of single legged knee extensor exercise at 80 % of their one repetition maximum. Muscle biopsy samples were obtained from the quadriceps muscle of both the control and exercised legs 2.5 h after completion of the exercise bout. Expression levels of the IGF-I mRNA transcripts were determined using real-time quantitative RT-PCR with specific primers. The resting levels of MGF were significantly (approximately 100-fold) lower than those of the IGF-IEa isoform. No difference was observed between the resting levels of the two isoforms between the two subject groups. High resistance exercise resulted in a significant increase in MGF mRNA in the young, but not in the elderly subjects. No changes in IGF-IEa mRNA levels were observed as a result of exercise in either group. The mRNA levels of the transcription factor MyoD were greater at rest in the older subjects (P < 0.05), but there was no significant effect of the exercise bout. Electrophoretic separation of myosin heavy chain (MHC) isoforms showed the older subjects to have a lower (P < 0.05) percentage of MHC-II isoforms than the young subjects. However, no association was observed between the composition of the muscle and changes in the IGF-I isoforms with exercise. The data from this study show an attenuated MGF response to high resistance exercise in the older subjects, indicative of age-related desensitivity to mechanical loading. The data in young subjects indicate that the MGF and IGF-IEa isoforms are differentially regulated in human skeletal muscle.
iemand die het wil samenvatten?
Ik zal het even voor je samenvatten.

MGF werkt niet...punt.

Nou, dat was makkelijk te lezen huh :D
Ik zal het even voor je samenvatten.

MGF werkt niet...punt.

Nou, dat was makkelijk te lezen huh :D

Icm IGF en op 300mcg dosering per week wel!
Je weet nooit of het werkt want er zijn weinig mensen hier die alleen MGF hebben gebruikt en vervolgens niks anders hebben gebruikt voor een jaar of zelfs nog langer alleen dan weet je of het werkelijk resultaat geeft.

Ikzelf heb het gebruikt en merkte dat me spiergroep waarin ik injecteerde sneller herstelde ik zette 100mcg PWO in elke spier (100links 100rechts) Of ik hier spiermassa van heb gekregen zou het niet weten, maar het doet zeker wat.
Als je weet wat MGF is, dan weet je ook dat je het de dag erna ook nog eens moet injecteren in de groep die je de dag ervoor heb getraind.
Wat waren je resultaten?

Ik heb het niet gebruikt. Quote is volgens een gozer uit de tekst die het wel heeft gebruikt.
Ik wacht wel eerst totdat jij het gebruikt hebt oke.:D
Ik heb het niet gebruikt. Quote is volgens een gozer uit de tekst die het wel heeft gebruikt.
Ik wacht wel eerst totdat jij het gebruikt hebt oke.:D

Niet normaal zo vroeg als jij op bent of wel?

Liefst dat jij eerst gekke shit gebruikt, ik ben meer iemand die achter de menigte aanloopt:D
MGF is bagger imo zelfs op 500mcg ed. gelukkig was het voor nop anders was ik er wel doodziek van geweest.

MGF is bagger imo zelfs op 500mcg ed. gelukkig was het voor nop anders was ik er wel doodziek van geweest.


dat is idd een behoorlijke dosering!
MGF is bagger imo zelfs op 500mcg ed. gelukkig was het voor nop anders was ik er wel doodziek van geweest.


Had je hat dan ook samen met IGF1 gebruikt?
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