Ultimate IGF-1 Guide

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    Ultimate IGF-1 Guide

    **I believe this thread was deleted during the switching of servers, so I will repost it & then some....***

    Meso's IGF-1 Guide
    Author Unknown

    IGF1, also known as somatomedin C, is polypeptide hormone about the same size as insulin. It is produced predominantly in the liver in response to growth hormone (GH) release from the pituitary gland. Many of the growth promoting effects of GH are due to its ability to release IGF1 from the liver. The conversion ratio of GH to IGF1 varies greatly in different individuals but most external sources of GH convert around 4-6mcg of IGF per one I.U. of GH. IGF-1 acts on several different tissues to enhance growth. IGF1 belongs in the 'superfamily' of substances known as 'growth factors,' along with epidermal (skin), transforming; platelet derived fibroblast, nerve, and ciliary neurotrophic growth factors. None of the other factors have any bearing on exoskeletal tissue incidentally however These agents all have in common the ability to stimulate cell division, known as mitogenesis, and cell differentiation. Meaning That In the case of IGF1 which does act on muscle tissue it will initiate the growth of new muscle fibers, and subsequently new receptors for testosterone. Users have unanimously concluded that it enhances cycles of steroids significantly. They also seem to be adamant about its ability to reduce fat and improve vascularity a great deal.

    The IGF1 Hype

    There is a considerable amount of hype surrounding IGF1. Every one is blaming the distended bellies of modern Bodybuilders on it. Also the freaky proportions that old bodybuilders that have been around for years are starting to attain. Anti-aging proponents are touting it as the miracle cure for every thing from Parkinson's disease to Alzheimer's. And the medical community has published numerous articles on it for its ability to cause cancer, diabetes and gigantism. While at the same time performing documented experiments on thousands of patients of muscle wasting diseases. And reporting significant turnabouts in there conditions. So what is a guy to think about IGF1 as far as athletic enhancement is concerned? Well first of all you need to know that most experiments conducted with IGF1 do not list the type of IGF used. I have written Dr. Robert Saline of the Swedish rejuvenation institute on several occasions and we have had in-depth discussions on the subject of IGF1 for physical appearance enhancement. He feels it would be unethical to prescribe IGF1 to a bodybuilder to increase muscle mass simply due to the fact that IGF1 has valid applications in the medical community, (Like I could give a rats ass about "ethical"). He can not argue that it is extremely effective as a promoter of muscle growth far beyond what androgens (steroids) alone can offer. Well fortunately in America IGF1 is not a drug (yet) and the FDA has no control over it as of now. This will change in the very near future however, Im absolutely sure of it.

    How to use IGF1

    Assuming that you have acquired legitimate IGF1 (R3) long chain, That's IGF1 with the binding protein added. You should take dosages ranging from 60mcg up to 120mcg per day in divided doses. One injection in the morning and again at bed time. Never exceed 120mcg in one day. IGF1 can cause serious gastrointestinal problems such as tumors intestinal swelling diarrhea and vomiting. Most IGF1 comes in a concentration of 1000mcg per ML or CC so it makes it easy to measure in an insulin syringe. 10 IU on the syringe is 100mcg. Do the math.

    IGF + Insulin

    If you plan on doing IGF1 with Insulin, listen closely IGF1 is not that expensive, sure you can get away with using less by including insulin in the stack, but IGF1 and Insulin together have a pro-insulin effect on your blood sugar balance. It can enhance the chances of a hypoglycemic episode ten fold. I would recommend against it for any one not ABSOLUTLY comfortable with insulin or IGF1.

    Here is how insulin and IGF1 work together. Igfbp3 is the binding protein, which allows IGF1 to remain active in the system for a long enough period of time to really work its magic. IGF1 by nature has a half-life of less than 10 minutes by its self. The molecule was so small it would escape the blood stream very rapidly. This was the reason IGF1 was so "underground". It took very frequent injections at high dosages to achieve even minimal results. Aside from this reconstituting the compound required a degree in biochemistry. This short acting version was the only IGF1 known until recently IGF1 would have been administered in 100 mcg dosages 4-6 times a day. That is a hell of a lot of IGF1. That explains a lot of the distended bellies. Now with R3 long chain IGF1 and the Binding protein IGFBP3 IGF1 will last up to 6 hours in the system. By binding IGF to the IGFBP3 you make the molecule larger and it gets trapped in the blood stream until the protein is broken down and the IGF molecule escapes. You can further its life by combining Insulin with it, although I here its very risky. Insulin prevents the breakdown of IGFBP3 and leaves the IGF1 molecule roaming free in the blood stream for longer periods of time up to 12 hours as insulin levels return to normal IGFBP3 will begin to break down and the IGF1 will escape from its bound protein IGFBP3 again having a half life of less than 10 minutes.

    Insulin should be taken at the normal dosage it is usually administered at minus 10% about 45 minutes prior to the IGF1 infusion. Again let me remind you this can be deadly if you don't know what you are doing. And of course do not use Insulin for the nighttime injection of IGF1 by taking it in the morning you prolong the IGF1's half life to 12 hours and then take a 6 hour injection, you should be fine. Hell if you want to eat a big bowl of rice and drink another 100g of simple carbs 45 minutes before the bed time IGF1 infusion you could spike insulin for at least a few hours of extended IGF1 activity. If your not going to be using insulin in the stack then go ahead and do the same in the morning.

    What users report

    Users of IGF1 have reported various results but all along the same lines, It does not appear to be dramatically less effective in any one individual (at least not to the best of my knowledge). I have a good friend who had to stop taking IGF1 due to stomach illness that was completely unrelated But he to experienced good gains from it for the 2 weeks he was on it, his dosage was 120mcg per day. One hour after the first injection he went to the gym and immediately told me about the uncontrollable pump he got from just one set.

    That would indicate to me that he was experiencing some form of cell volumization. The general consensus on IGF1 seems to be that its benefits are as fallow:

    Increased Pump Pumps are reported to be so severe that workouts are often cut short due to lack of ability to the muscle through the full range of motion...ouch

    Gains retention is increased if IGF is used in a cycle I am not sure why, but IGF1 seems to make gains on a cycle stick with virtually no post cycle loss. Every bodybuilder I've spoken with seems to think this for some reason. Most of them use drugs like Anadrol or Dianabol with it because of the amount of size attained with these drugs. The usual draw back to these drugs is that in most users there is a post cycle "crash" that occurs, so the reasoning is to toss IGF1 into the stack and grow larger faster with out the post cycle crash blues.

    Reverses testicular atrophy

    Testicles if shrunken will return to "full swing" so to speak even in the middle of a cycle. If not shrunken they will not shrink during the cycle. This may explain partially why gains are kept after the cycle.


    Users report feeling drained and tired all day. This seems to be one of the negative side effects to IGF1, it will make you sleep longer and you will require more sleep at night to feel rested for the morning. This is common with high doses of HGH and exhibited in children, whose IGF1 levels are extraordinarily high. A child needs 4 hours more sleep than an adult on average does. This may be directly or indirectly related to IGF1 levels.


    An almost arthritic feeling is commonly associated with high levels of HGH, well IGF1 has the exact same property. IGF1 will cause your hands, fingers and knuckles to ache this is one way you can be sure you got real IGF1.

    IGF-1's Side effects

    Every thing has a down side. To bake a cake ya gotta brake an egg. IGF1 is no exception. The drug used in larger quantity around the 100mcg+ range will cause headaches, occasional nausea and can contribute to low blood sugar or hypoglycemia in some users. Although I have never heard of this first hand I'm sure its true.

    IGF1 will attach its self to the lining of the intestine and cause atrophy of the gut. Every thing IGF1 touches will grow and you have a lot of receptors on the lining of the large intestine and inner wall of the abdominal well. This is what causes the GH gut look. You can easily avoid this by limiting your dosages and cycle lengths. IGF1 cycles should be kept to 4-6 weeks with 4-6 weeks off in-between. IGF-1 is considerably more powerful than HGH and you need to think of it along those lines as far as dosing goes. We all know what to much HGH can do over prolonged periods of usage. The Neanderthal look is definitely not going to win any shows this year. I would recommend 80 mcg a day for 4 weeks at a time you should get good results from that for a while. I don't know if you will need to up the dosage at any point, but I would think in the case of IGF1 it wouldn't matter. If 80mcg doesn't do it for ya, then bump it up to 100 You should definitely feel it at this point If not suspect the IGF1 as being fake. Beyond 120 mcg per day your asking for trouble, This compound demands as much respect as its sister amino Insulin.

    Clinical Facts about IGF-1

    IGF-1 is a polypeptide of 70 amino acids (7650 daltons), and is one of a number of related insulin-like growth factors present in the circulation. The molecule shows approximately 50% sequence homology with proinsulin and has a number of biological activities similar to insulin. IGF-1 is a mediator of longitudinal growth in humans or how tall you are capable of becoming. Serum IGF-1 concentrations are altered by age, nutritional status, body composition, and growth hormone secretion. A single basal IGF-1 level is useful in the assessment of short stature in children and in nutritional support studies of acutely ill patients. For the diagnosis of acromegaly, a single IGF-1 concentration is more reliable than a random hGH measurement (Oppizi, et al., 1986). IGF-1 can be used for the assessment of disease activity in acromegaly (Barkan, et al., 198.

    Almost all (>95%) of serum IGF-1 circulates bound to specific IGF binding proteins (IGFBPs), of which six classes (IGFBPs 1-6) have been identified (Rudd, 1991). BP3 is thought to be the major binding protein of IGF-1

    IGF-1 Once Again Proves to be One of the Most Powerful Mediators of Muscle Growth

    As we approach the new millennium we find the science of building muscle progressing faster than ever before. Long gone are the days of simple trial and error when it comes to building muscle. The modern bodybuilder demands more than just "hear say" if they are to adopt a new training routine or nutritional supplement. This column was created to keep today’s bodybuilder on the cutting edge of scientific research that might benefit them in their quest for body perfection.

    Not since the travels of Juan Ponce de Leon has the fountain of youth seemed so close!
    Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function
    Elisabeth R. Barton-Davis*, Daria I. Shoturma*, Antonio Musaro, Nadia Rosenthal, and H. Lee Sweeney*,
    * Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA and Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA
    Proc Natl Acad Sci U S A 1998 Dec 22;95(26):15603-7

    Although the mechanisms underlying age associated muscle loss are not entirely understood, researchers attempted to moderate the loss by increasing the regenerative capacity of muscle. This involved the injection of a recombinant adeno-associated virus directing overexpression of insulin-like growth factor I (IGF-I) in differentiated muscle fibers.
    They demonstrated that the IGF-I expression promotes an average increase of 15% in muscle mass and a 14% increase in strength in young adult mice (Figure 1), and remarkably, prevents aging-related muscle changes in old adult mice, resulting in a 27% increase in strength as compared with uninjected old muscles (Figure 2). Muscle mass and fiber type distributions were maintained at levels similar to those in young adults. These results suggest that gene transfer of IGF-I into muscle could form the basis of a human gene therapy for preventing the loss of muscle function associated with aging and may be of benefit in diseases where the rate of damage to skeletal muscle is accelerated.
    I’m not sure where to begin. This study has the potential to completely change the way we age.
    In this experiment, a recombinant adeno-associated virus, directing overexpression of insulin-like growth factor I (IGF-I) in mature muscle fibers, was injected into the muscles of mice. The DNA that was originally in the virus was removed along with markers that stimulate immune response. DNA coding for IGF-1 was then put into the virus along with a promoter gene to ensure high rates of transcription. The results, as you can see by figures 1 & 2, were dramatic.
    IGF-1 plays a crucial role in muscle regeneration. IGF-1 stimulates both proliferation and differentiation of stem cells in an autocrine-paracrine manner, although it induces differentiation to a much greater degree. IGF-1, when injected locally, increases satellite cell activity, muscle DNA, muscle protein content, muscle weight and muscle cross sectional area. The importance of IGF-1 lies in the fact that all of its apparent functions act to induce muscle growth with or without overload although it really shines as a growth promoter when combined with physical loading of the muscle.

    IGF-1 also acts as an endocrine growth factor having an anabolic effect on distant tissues once released into the blood stream by the liver. IGF-1 possesses the insulin-like property of inhibiting degradation, but in addition can stimulate protein synthesis. The insulin-like effects are probably due to the similarity of the signaling pathways between insulin and IGF-1 following ligand binding at the receptors.
    The ability of IGF-I to stimulate protein synthesis resembles the action of GH, which was shown in separate studies on volunteers to stimulate protein synthesis without affecting protein degradation. Although it is often believed that the effects of GH are mediated through IGF-1, this cannot be the case entirely. First, the effects of the two hormones are different, in that GH does not change protein degradation. Second, the effect of GH is observed with little or no change in systemic IGF-1 concentrations. Age related muscle loss has been prevented with GH injections, however it is believed that this is accomplished through IGF-1.
    The results of this study are similar to other studies where IGF-1 was injected directly into muscle tissue, resulting in increases in size and strength of experimental animals. Using a virus as a genetic vehicle has an advantage over simply injecting the growth factor. The effects of a single viral treatment last significantly longer (months if not years) because the muscle cell itself is constantly overproducing its own IGF-1 from injected DNA.
    The fact that the IGF-1 produced by the muscle of these mice did not reach the blood stream is interesting. Systemic injections of IGF-1 have not been successful in inducing this kind of anabolic effect in humans. In addition, IGF-1 produced by the liver is genetically different than that produced by muscle tissue. It could be that providing additional DNA for the muscle to produce it’s own IGF-1 is the key to achieving anabolic and rejuvenative effects specifically in skeletal muscle.
    In this study there was a preferential preservation of type IIb muscle fibers in aging mice. These are the fibers most sensitive to muscle hypertrophy from training and they are also the first fibers to disappear with aging. In the mice receiving the engineered virus, there was also a preservation of the motor neuron, leading to an increase in functional capacity. It is speculated that age related muscle loss is secondary to the loss of neuronal activation of type-II fibers. By preventing the degeneration of typ-II motor units, functional capacity could be maintained into old age. This technique may also serve useful in the prevention of osteoporosis. Further study is necessary to determine wether IGF-1 is having an effect only on muscle fibers or on nervous tissues as well.
    Finally, it was also exciting to see muscle growth in the young mice who received the injection (15% increase in muscle mass). This means that the injection provided levels of IGF-1 far and above what the muscle normally has access to and not simply a preservation of normal levels. Remember that this was not combined with exercise. The growth of the injected muscles happened even without an extreme mechanical stimulus. The mice were simply allowed to run around as they usually do. Because of these dramatic results, the authors expressed concern about the use of this technique to enhance performance or cosmetic appearance. Research Update is not my personal soap box so I won’t go off on the gender centered hypocrisy of cosmetic enhancement in our society. All we can hope for is that this technique will be used to treat more important diseases such as muscular dystrophy and thereby become somewhat available for other uses as well.

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    IGF-1 Handbook
    From Bryan Haycock

    Bodybuilding is a gaudy demonstration of human accomplishment. The attitude that comes with it reminds me of the Baroque cathedrals of Europe where every inch of artistry shouts, "More is better"! At the same time, bodybuilding is a subculture, as well as a science. It is a multi-disciplinarian science including physiology, biology, endocrinology, metabolism, cellular physiology, genetics, molecular biology, and we mustn’t forget, pharmacology. The list of scientific fields pertaining to bodybuilding is extensive.

    I view bodybuilding contests as a county fair of sorts. When I ponder the present status of professional bodybuilding I often imagine seeing prize winning cattle being brought before hoards of voyeuristic onlookers, marveling at the spectacle of seeing something beyond what nature intended.

    As a bodybuilder I can’t help but think of all the time, energy, food, genetic tinkering and drugs that went into creating such an impressive muscle bound specimen. Here, at the fair, growing prize winning cattle is not a question of morality or ethics, but rather a manifestation of dedication, the proper application of knowledge, and perhaps a display of financial resources. The things done to the animal to make it grow bigger, leaner and faster are, for the most part, seen as beneficial. I hold bodybuilding in the same arena as this. Using drugs, and one day soon genetic tinkering, to grow the human body bigger, leaner, in half the time is not, in and of itself, a question of morality, but rather an exercise in scientific accomplishment. It is an expression of human understanding in the scientific fields heretofore mentioned in order to gain control of the natural world around us, or in this case, within us.

    So why is it that bodybuilding fails to be recognized as a legitimate area of scientific inquiry among most peer review scientific journals? The answer is complicated, certainly too philosophical to get into here. For our purposes lets just say that bodybuilding fails to present sufficient value to our society to be officially recognized as something worth devoting time and federal moneys to. In the mean time, scientists will continue to borrow from the tools and practices of bodybuilding to explore their own respective, and respected, areas of research. We as bodybuilders will have to be satisfied, for the time being, gathering up table scraps from laboratory bench tops to accomplish our goals.

    This article will present a holistic picture of some of the most recent scraps to fall our way from the halls of academia. The focus will be on the proper application of human growth hormone (GH) and insulin-like growth factor 1 (IGF-1) for the purpose of building muscle. This information will be presented in such a way as to describe how these growth factors might be incorporated into traditional protocols consisting mainly of androgens. It is important while reading this to remember that my perspective on bodybuilding will undoubtedly effect the way I present this information. I do not in any way condone cheating to win a contest, or breaking state or federal laws to accomplish your goals. Instead, I am simply sharing knowledge with current, or potential, users with appropriate access to anabolic substances.


    The GH/IGF-1 Axis

    Your body’s GH levels are tightly regulated by numerous chemical messengers including macronutrients, neurotransmitters, and hormones. The signal to increase your body’s GH levels starts in the hypothalamus. There, two peptide hormones act in concert to increase or decrease GH output from the pituitary gland. These hormones are somatostatin (SS) and growth hormone-releasing hormone (GHRH). Somatostatin acts at the pituitary to decrease GH output. GHRH acts at the pituitary to increase GH output. Together these hormones regulate, in pulsatile fashion, the level of GH you have floating around in your body (see Fig. 1).

    Several factors can effect this delicate balance. First, GH is subject to negative feedback in response to its own release. GH, as well as IGF-1, circulate back to the hypothalamus and pituitary to increase SS release, thereby decreasing GH release. GH may also act in an autocrine and paracrine (i.e. Effecting the source cells and neighboring cells without having to enter the circulation) fashion within both the hypothalamus and pituitary.

    Neurotransmitters also effect GH levels at the hypothalamus. This neuroendocrine control is still being elucidated but some factors are already clearly involved (see table 1).

    Table 1.

    Neurotransmitter system Effect on GH Neurotransmitter or drug









    Cholinergic Increase Acetylcholine
    Opioids Increase Morphine
    Dopamine Increase L-Dopa
    Gut-brain peptides Increase

    Nutrition and metabolic factors also modulate GH levels. A fall in blood glucose such as during exercise or during sleep causes an increase in GH secretion. High protein feedings increase acute GH secretion. Some amino acids such as L-arginine seem to increase GH by decreasing SS release from the hypothalamus. Even the vitamin Niacin has been shown to increase exercise induced GH release by 300- 600%(Murray, 1995). In this particular study there were four separate trials where 10 subjects cycled at 68% VO2 max for 120 min followed by a timed 3.5-mile performance task. Every 15 min during exercise, subjects ingested 3.5 ml./kg lean body weight of one of four beverages: 1) water placebo (WP), 2) WP + 280 mg nicotinic acid.l-1 (WP + NA), 3) 6% carbohydrate-electrolyte beverage (CE), and 4) CE + NA. Ingestion of nicotinic acid (WP + NA and CE + NA) blunted the rise in free fatty acids (FFA) associated with WP and CE; in fact, nicotinic acid ingestion effectively prevented FFA from rising above rest values. The low FFA levels with nicotinic acid feeding were associated with a 3- to 6-fold increase in concentrations of human growth hormone throughout exercise. The question remains, does this dramatic, yet temporary, increase in GH lead to a greater training effect? It may lead to greater glycogen storage capacity but other than that, we really don’t know.

    Caloric restriction dramatically reduces serum levels of IGF-1 yet at the same time increases GH release. This mechanism effectively helps the individual adapt metabolically without having anabolic actions which would potentially hasten death by starvation. It is important to understand that GH can either be anabolic or catabolic. When nutrient intake is high, GH secretion is increased leading also to increased levels of IGF-1, IGFBP3 and insulin. The main role of GH under these conditions is to increase anabolism through local growth factors like IGF-1 and insulin. Conversely, when nutrient intake is low, GH is again increased. But this time there is no concomitant increase in IGF-1, IGFBP3, or insulin. Under these circumstances GH is acting as a catabolic hormone increasing the utilization of fat for fuel thus sparing body glucose yet having no muscle building effects. This behavior of the GH/IGF-1 axis is part of what makes it so difficult to build muscle while dieting. It should be noted that locally produced IGF-1 in skeletal muscle responds normally to training while dieting. This makes heavy poundages a must when trying to get ready for a show without the use of drugs.


    Growth Hormone: How does it work?

    It is always prudent to have a basic understanding of how a supplement, hormone or drug works to build and/or preserve muscle before considering its use. The knowledge of how a hormone acts in the body is necessary to make your own decisions and manage your own regimens if you plan on utilizing it. Without this understanding you will no doubt end up wasting a lot of money and perhaps put your health at risk.

    It has been long believed that GH exerts its anabolic effects on peripheral tissues through IGFs, also known as somatomedins ("mediator of growth"). Binding proteins play an important role in moderating the anabolic effects of both GH and IGF-1. IGF-1 is controlled by at least 6 different binding proteins and there may others waiting to be elucidated. To date there are a couple theories as to just how GH causes growth in target tissues. The first theory is called the somatomedin hypothesis (Daughaday, 1972).

    The Somatomedin hypothesis states that GH is released from the pituitary and then travels to the liver and other peripheral tissues where it causes the synthesis and release of IGFs. IGFs got there name because of there structural and functional similarity to proinsulin. This hypothesis dictates that IGFs work as endocrine growth factors, meaning that they travel in the blood to the target tissues after being released from cells that produced it, specifically the liver in this case. Indeed, many studies have followed showing that in animals that are GH deficient, systemic IGF-1 infusions lead to normal growth. The effects were similar to those observed after GH administration. Interestingly, additional studies also followed that showed IGF-1 to be greatly inferior as an endocrine growth factor requiring almost 50 times the amount to exert that same effects of GH (Skottner, 1987). Recently rhIGF-1 has become widely more available and is currently approved form the treatment of HIV associated wasting. This increased availability allowed testing of this hypothesis in humans. Studies in human subjects with GH insensitivity (Laron syndrome) has consistently validated the somatomedin hypothesis (Rank, 1995; Savage, 1993).

    The second theory as to how GH produces anabolic effects is called the Dual Effector theory (Green, 1985). This theory states that GH itself has anabolic effects on body tissues without the need of IGF-1. This theory has been supported by studies injecting GH directly into growth plates. Further evidence supporting this theory lies in genetically altered strains of mice. When comparing mice who genetically over express GH and mice who over express IGF-1, GH mice are larger. This evidence has been sited by some to support the dual effector theory. Interestingly, when IGF-1 antiserum (it destroys IGF-1) is administered concomitantly with GH, all of the anabolic effects of GH are abolished.

    The Somatomedin theory and the Dual Effector theory are not all that different. One simply asserts that GH can produce growth without IGF-1. From the research I am inclined to believe in the Somatomedin theory. This only becomes an issue when one decides whether or not to use just GH or to combine it with IGF-1 or insulin.

    From the evidence currently available you can count on three major mechanisms by which GH leads to growth (Spagnoli, 1996).

    The effects of GH one bone formation and organ growth are mediated by the endocrine action of IGF-1. As stated in the Somatomedin hypothesis, GH, released from the pituitary, causes increased production and release of IGF-1 into the general circulation. IGF-1 then travels to target tissues such as bones, organs, and muscle to cause anabolic effects.
    GH regulates the activity of IGF-1 by increasing the production of binding proteins (specifically IGFBP-3 and another important protein called the acid-labile subunit) that increase the half-life of IGF-1 from minutes to hours. Circulating proteases then act to break up the binding protein/hormone complex thereby releasing the IGF-1 in a controlled fashion over time. GH may even cause target tissues to produce IGFBP-3 increasing its effectiveness locally.
    IGF-1 not only has endocrine actions, but also paracrine/autocrine actions in target tissues. This means that as GH travels to my muscles, the muscle cells increase there production of IGF-1. This IGF-1 may then travel to adjacent cells (especially satellite cells) leading to growth and enhanced rejuvenative ability of cells that didn’t see any GH. This is as suggested by the Dual Effector theory.


    IGF-1: How does it work?

    To understand how IGF-1 works you have to understand how muscles grow. The ability of muscle tissue to constantly regenerate in response to activity makes it unique. It’s ability to respond to physical/mechanical stimuli depends greatly on what are called satellite cells. Satellite cells are muscle precursor cells. You might think of them as "pro-muscle" cells. They are cells that reside on and around muscle cells. These cells sit dormant until called upon by growth factors such as IGF-1. Once this happens these cells divide and genetically change into cells that have nuclei identical to those of muscle cells. These new satellite cells with muscle nuclei are critical if not mandatory to muscle growth.

    Without the ability to increase the number of nuclei, a muscle cell will not grow larger and its ability to repair itself is limited. The explanation for this is quite simple. The nucleus of the cell is where all of the blue prints for new muscle come from. The larger the muscle, the more nuclei you need to maintain it. In fact there is a "nuclear to volume" ratio that cannot be overridden. Whenever a muscle grows in response to functional overload there is a positive correlation between the increase in the number of myonuclei and the increase in fiber cross sectional area (CSA). When satellite cells are prohibited from donating new nuclei, overloaded muscle will not grow (Rosenblatt,1992 & 1994; Phelan,1997). So you see, one important key to unnatural muscle growth is the activation of satellite cells by growth factors such as IGF-1.

    IGF-1 stimulates both proliferation (an increase in cell number) and differentiation (a conversion to muscle specific nuclei) in an autocrine-paracrine manner, although it induces differentiation to a much greater degree. This is in agreement with the Dual Effector theory. In fact, you can inject a muscle with IGF-1 and it will grow! Studies have shown that , when injected locally, IGF-1 increases satellite cell activity, muscle DNA content, muscle protein content, muscle weight and muscle cross sectional area (Adams,1998).

    On the very cutting edge of research scientists are now discovering the signaling pathway by which mechanical stimulation and IGF-1 activity leads to all of the above changes in satellite cells, muscle DNA content, muscle protein content, muscle weight and muscle cross sectional area just outlined above. This research is stemming from studies done to explain cardiac hypertrophy. It involves a muscle enzyme called calcineurin which is a phosphatase enzyme activated by high intracellular calcium ion concentrations (Dunn, 1999). Note that overloaded muscle is characterized by chronically elevated intracellular calcium ion concentrations. Other recent research has demonstrated that IGF-1 increases intracellular calcium ion concentrations leading to the activation of the signaling pathway, and subsequent muscle fiber hypertrophy (Semsarian, 1999; Musaro, 1999). I am by no means a geneticist so I hesitated even bringing this new research up. In summary the researchers involved in these studies have explained it this way, IGF-1 as well as activated calcineurin, induces expression of the transcription factor GATA-2, which accumulates in a subset of myocyte nuclei, where it associates with calcineurin and a specific dephosphorylated isoform of the transcription factor nuclear factor of activated T cells or NF-ATc1. Thus, IGF-1 induces calcineurin-mediated signaling and activation of GATA-2, a marker of skeletal muscle hypertrophy, which cooperates with selected NF-ATc isoforms to activate gene expression programs leading to increased contractile protein synthesis and muscle hypertrophy. Did you get all that?

    In this the first part of "Growing beyond what nature intended" we have discussed the role, function and interaction of growth hormone and insulin-like growth factor-1 in tissue growth. This is referred to collectively as the GH/IGF-1 axis. We learned that this axis is controlled by negative feedback meaning that GH, after being released, circulates back to the hypothalamus and pituitary to effectively stop further GH release. We learned that circulating IGF-1 has the same inhibiting effect on GH release. We discussed very briefly the role of neurotransmitters in regulating GH release through growth hormone releasing hormone (GHRH) and somatostatin (SS). We even touched on the nitty gritty details of just how IGF-1 does its magic on muscle cells. I’m afraid I may have disappointed a few of you waiting for the "how to" section of this article. Never fear, in part II you will learn about the effects of these hormones as well as androgens, insulin and thyroid hormones when given, individually and combined, to previously healthy individuals. I will remind you that this article is not intended to encourage you put your health at risk, or to break the law by acquiring and using these substances illegally. As always, the goal Meso-Rx is not to condone the use of performance enhancing substances, but to educate by providing unbiased information about all aspects of high level sport performance and bodybuilding.

    Part II: Role of Androgens on GH Secretion and IGF-1 Sensitivity


    Selected References:

    Murray R, Bartoli WP, Eddy DE, Horn MK. Physiological and performance responses to nicotinic-acid ingestion during exercise. Med Sci Sports Exerc 1995 Jul;27(7):1057-62

    Daughaday WH., Hall K., Raben MS., et al: Somatomedin: A proposed designation for the "sulfation factor" Nature 235:107, 1972

    Skottner A., Clark RG., Robinson ICAF., et al: Recombinant human insulin-like growth factor: Testing the Somatomedin hypothesis in hypophysectomized rats. J Endocrinol 112:123 1987

    Rank MB., Savage MO., Chatelain PG., et al: Insulin-like growth factor improves height in growth hormone insensitivity: Two year’s result. Horm Res 44:253, 1995

    Savage MO., Blum WF., Ranke MB., et al: Clinical features and endocrine status in patients with growth hormone insensitivity (Laron syndrome). J Clin Endocrinol Metab 77:1465, 1993

    Green H., Morikawa M., Nixon T. A dual effector theory of growth hormone action. Differentiation 29:195, 1985

    Spagnoli A, Rosenfeld RG. The mechanisms by which growth hormone brings about growth. The relative contributions of growth hormone and insulin-like growth factors. Endocrinol Metab Clin North Am 1996 Sep;25(3):615-31

    Phelan JN, Gonyea WJ. Effect of radiation on satellite cell activity and protein expression in overloaded mammalian skeletal muscle. Anat. Rec. 247:179-188, 1997

    Rosenblatt JD, Parry DJ., Gamma irradiation prevents compensatory hypertrophy of overloaded extensor digitorum longus muscle. J. Appl. Physiol. 73:2538-2543, 1992

    Rosenblatt JD, Yong D, Parry DJ., Satellite cell activity is required for hypertrophy of overloaded adult rat muscle. Muscle Nerve 17:608-613, 1994

    Adams GR, McCue SA., Local infusion of IGF-1 results in skeletal muscle hypertrophy in rats. J. Appl. Physiol. 84(5): 1716-1722, 1998

    Dunn SE., Burns JL., & Michel RN. Calcineurin is required for skeletal muscle hypertrophy. J. Biol. Chem. 274(31):21908-21912, 1999

    Semsarian C, Wu MJ, Ju YK, Marciniec T, et al. Skeletal muscle hypertrophy is mediated by a Ca2+-dependent calcineurin signaling pathway. Nature 1999 Aug 5;400 (6744) :576-81

    Musaro A, McCullagh KJ, Naya FJ, Olson EN, Rosenthal N. IGF-1 induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1. Nature 1999 Aug 5;400(6744):581-5
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    IGF-1 & Its potential abuse by athletes

    Insulin-like growth factor in muscle growth and its potential abuse by athletes
    Gregory R Adams1
    1 Department of physiology and biophysics University of California, Irvine Irvine, CA 92717-4560

    Skeletal muscle is an inherently plastic tissue. Evidence suggests that muscles are constantly adapting in both quantity and quality to the changing functional demands imposed by the types and amounts of physical activity routinely performed. To date, the evidence suggests that in adults, activity-induced adaptations of skeletal muscle are orchestrated by local—that is, tissue-level as opposed to systemic—mechanosensitive mechanisms, which appear to include several growth factors and hormones. Of particular recent interest is the growth hormone (GH) and insulin-like growth factor-I (IGF-I) system. In the context of skeletal muscle homoeostasis, IGF-I is thought to mediate most of the growth-promoting effects of circulating GH. In addition, it appears to function in a GH-independent autocrine-paracrine mode in this tissue.1

    As information on the mechanisms that modulate muscle adaptation becomes available in the scientific literature, it is tempting for athletes to apply this knowledge to enhance muscle mass, and hence function, by artificially manipulating these systems. In some cases, this misapplication of information has led to the simplistic notion that exogenous anabolic agents can be used to safely and effectively stimulate or augment muscle. Unfortunately, many of these attempts have been unsuccessful, and in truth, they ignore our understanding of the integrated nature of physiologic systems.

    The most obvious problem with misusing anabolic substances is that they are invariably nonspecific. Agents that can stimulate muscle cells to hypertrophy will undoubtedly have effects on other cells and tissues—for example, the effects of GH on prostatic hypertrophy. Another problem is that just as the body is made up of tissues and organs that function as an integrated whole, so muscle comprises different cell types that must also function in unison. For example, a treatment that stimulates muscle cells to hypertrophy must also recruit fibroblasts to strengthen the connective tissues that will transmit the force generated by the muscle cells and must enhance angiogenesis and mitochondrial function. Without this coordination, larger (therefore stronger) muscle cells may develop, but the application of this enhanced contractile function would only damage the structure of the muscle when the unenhanced connective tissue fails.

    Results from animal studies are instructive with regard to manipulating IGF-I either directly or through GH. Researchers have long sought ways to mitigate the atrophy-inducing effects of unloading on skeletal muscle. An animal model used to study this effect involves suspending rats by their tails with only their front feet touching any surface of the cage. The muscle atrophy that results mimics that seen in humans after space flight. When GH or IGF-I has been supplied exogenously during tail suspension, the results indicated that the mass of the normally weight-bearing muscles was, in fact, conserved. Owing to the effects of these treatments on other tissues, however, the overall body weight of the rats had increased. It was as if the growth and development program from an earlier developmental stage had been reactivated. When compared with their body weight changes, however, the muscles had actually grown less—that is, the normalized muscle mass was less in treated than untreated animals—the end result being that the IGI-I-treated rats would actually be less well adapted to normal ambulatory activity than the rats that received no treatment at all.

    In humans, the effects of attempts to augment muscle mass using IGF-I have been less dramatic. In studies designed to overcome the loss of muscle in the elderly, the overall effect of increasing circulating IGF-I levels experimentally has been negligible.2,3,4 In 1 study, the investigators managed to double the circulating IGF-I levels in elderly subjects but found no effect on the rate of protein synthesis in muscles and no augmentation of strength.4 In addition to this disappointing result, the supplementation of IGF-I in otherwise healthy—that is, GH-normal—people is associated with moderate-to-severe hypoglycemia (it is, after all, insulin-like),5 decreased GH secretion,6,7 a shift from lipid to carbohydrate oxidation for energy,7 and a general disruption of the insulin-glucagon system.5,7 The issue of augmenting IGF-I is rendered even more complex because the biologic activity of IGF-I in the body is substantially influenced by the family of IGF-binding proteins.8 For example, recent work on the effects of hypoxia on rat growth suggests that it is the effect of IGF-binding protein-3 that is more closely related to overall growth than is IGF-I itself.9

    A more troubling aspect of IGF-I has recently emerged. In addition to a direct anabolic effect on skeletal muscle—for example, the production of more protein—IGF-I is also capable of stimulating the proliferation and differentiation of muscle stem cells (satellite cells). Results of animal studies suggest that this process is obligatory for muscle hypertrophy to proceed. Evidence that IGF-I is mitogenic should serve as a cautionary note to those who would use this agent to promote an anabolic state. Additional evidence suggests that IGF-I signaling may also participate in cellular transformation.10 Specifically, elevated IGF-I levels have been linked to prostate, colorectal, and lung cancers.11

    Given its potentially adverse effects, ranging from disruption of the insulin system to cancer, the exogenous augmentation of IGF-I is not an attractive or effective method of increasing muscle mass or function. Clearly, a prerequisite to the therapeutic use of these powerful growth factors is focused research on the mechanisms through which these mediators actually influence growth in the context of the whole organism.


    Adams GR. The role of IGF-I in the regulation of skeletal muscle adaptation. Exerc Sport Sci Rev 1998; 26: 31 -60.[Medline]
    Taaffe DR, Jin IH, Vu TH, et al. Lack of effect of recombinant human growth hormone (GH) on muscle morphology and GH-insulin-like growth factor expression. J Clin Endocrinol Metab 1996; 81: 421 -425.[Abstract]
    Taaffe DR, Pruitt L, Reim J, et al. Effect of recombinant human growth hormone on the muscle strength response to resistance exercise in elderly men. J Clin Endocrinol Metab 1994; 79: 1361 -1366.[Abstract]
    Yarasheski KE, Zachwieja JJ, Campbell JA, et al. Effect of growth hormone and resistance exercise on muscle growth and strength in older men. Am J Physiol 1995; 268: E268 -E276.[Medline]
    Jenkins PJ. Growth hormone and exercise. Clin Endocrinol 1999;50: 683 -689.[Medline]
    Carroll PV, Umpleby M, Alexander EL, et al. Recombinant human insulin-like growth factor-I (rhIGF-I) therapy in adults with type 1 diabetes mellitus: effects on IGFs, IGF-binding proteins, glucose levels and insulin treatment. Clin Endocrinol 1998; 49: 739 -746.[Medline]
    Sherwin RS, Borg WP, Boulware SD. Metabolic effects of insulin-like growth factor-I in normal humans. Horm Res 1994; 41 (suppl 2): 97 -102.[Medline]
    Baxter, RC. Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities. Am J Physiol 2000;278: E967 -E976.
    Moromisato DY, Moromisato MY, Brasel JA, et al. Effect of growth hormone therapy in mitigating hypoxia-induced and food restriction-induced growth retardation in the newborn rat. Crit Care Med 1999; 27: 2234 -2238.[Medline]
    Baserga, R. The IGF-I receptor in cancer research. Exp Cell Res 1999;253: 1 -6.[Medline]
    Grimberg A, Cohen P. Role of insulin-like growth factors and their binding proteins in growth control and carcinogenesis. J Cell Physiol 2000;183: 1 -9.[Medline

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