Human growth hormone (Somatotropin) is produced in the body by the pituitary gland. Before this happens, Growth Hormone Releasing Hormone (HGHRH) and Somatostatin (SST) are released by the hypothalamus, and that determines whether more or less HGH is produced by the pituitary.(1) Many factors influence the release of HGH, however, including nutrition and exercise (6)(7).
Once it is released, Human Growth Hormone (HGH), which is also called Somatotropin (STH) has many functions in the human body. HGH is a protein that stimulates the body cells to increase both in size, as well as undergo more rapid cell division than usual. In addition, it enhances the movement of amino acids through cell membranes and also increases the rate at which these cells convert these molecules into proteins. Clearly, you can see that this would amount to an anabolic (muscle building) effect in the human body. HGH also has the ability to cause cells to decrease the normal rate at which they utilize carbohydrates, and simultaneously increase the rate at which they use fats.(1) Fat loss and lean mass increases with HGH have been found at a dose as low as . 0.028 iu/kg/daily for 24 weeks (4), however, in my estimation, that would be insufficient for a bodybuilder trying to gain muscle. Let´s use .028iu/kg as a working number; that´s 2.8iu for a 100kg (220lbs) bodybuilder. That´s certainly not unreasonable, and I would say that that dose to 2x that dose is the range most bodybuilders and athletes are finding their best results with. Also, that length of time used in the study I just mentioned (24 weeks) is very typical of HGH use, and in conversations with my friends who have used this compound, have told me that they experience consistent results starting well after the 2-month-mark, and they tend to either run this stuff for 6 months at a time, or year-round (if they have sufficient funds). One of my friends is able to consistently retain a shredded 6-7% body fat all year round with the assistance of HGH, whether he is on steroids or off. He also has noted that his cardio (fast walking, for an hour a day) was much easier while on HGH than when off, and certainly the research I´ve done would support his claim that sub maximal aerobic ability is improved with HGH use (5) (15).
How anabolic is this stuff? Well, even endurance athletes at rest (!) were observed in one study to be in an anabolic state (8). Yeah, so you can basically run marathons and take this stuff, and still build some muscle. Pretty impressive, right?
Growth Hormone is usually secreted in rhythmic pulses while you are sleeping, as two peptides, HGHRH and Somatostatin (SST) are alternately released. As you can guess, HGHRH (Growth Hormone Releasing Hormone) is the one responsible for the Release of Growth Hormone (And who said scientists have funny ways for naming things.(1)
Growth hormone also has the ability to stimulate the production (or reproduction, in the case of an injury) of cartilage. This, however, requires the presence of a mediator substance, Somatomedin (IGF), which is released from the liver in response to HGH, and the IGF, in turn, actually promotes the growth of cartilage.(1)
Although it requires IGF to actually grow new cartilage, HGH is directly able to stimulate the elongation of bone tissue.(1), and HGH has also been shown to elicit a positive effects on erythropoeisis (9), which is great for both anabolism as well as endurance.
Remember the negative feedback loop I always tell you about? Well, of course, your body has one which can stop the secretion of HGH, and it involves IGF. When your liver receives secretes IGF-1, it sends a message to both your Hypothalamus as well as your Pituitary to stop producing HGH. (1)
As you have probably guessed by now, your body produces the majority of it´s HGH during your early years, when you are experiencing growth spurts. As you get older, however, you just produce less of this stuff, and its effects are much less pronounced. This was the driving force behind the (always weird) life-extension crowd embracing HGH in the early 90´s. And, as usual, the driving force behind the athletic world embracing HGH was Dan Duchaine, which I´m sure comes as no surprise to many. He first wrote a teaser about it in his Underground Steroid Handbook, and then wrote extensively about it for the next couple of decades. At that time, Grorm, was being used. This nasty stuff was HGH extracted from (are you ready?): the pituitary of dead bodies? That´s real “Dawn of the Dead” style science, in my opinion. I guess it´s an advance from a couple of centuries ago, when Descartes (the “I think therefore I am” guy) declared the pituitary the part of the human body where the soul resides. Anyway, back to the cadaver-thing, the HGH extracted from the cadavers was found to be able to (in rare cases) carry a rare brain disease. This of course, infected the kids who received the infected HGH. The use of HGH from cadavers was subsequently discontinued. Back then (the 80´s) there was also a fake version of some purple looking HGH going around (it was HCG I believe, mixed with B-12) called “Rhesus Monkey Growth Hormone”, which is pretty funny, looking back on it. To this day, however, if you get fake HGH, it´s still probably HCG, since both come presented as a powder and bacterioistatic water you need to use to reconstitute it (and then it needs to be refrigerated).
Even if you are using the non-cadaver-derived stuff (and at this point, I´m 100% sure that there´s none of the old Grorm left on shelves anywhere), it´s possible that you experience some side effects like carpal tunnel syndrome, acromegaly (a thickening or growth of bones, most noticeable in the feet, hands, and forehead), and enlarged organs. Gynocomastia is also possible as a side effect of HGH use, as well as Fluid retention (16) (the later being initially pointed out to me by a female colleague who had a pre-contest bodybuilder using HGH as part of his contest prep).
Now for some really interesting stuff:
Although HGH can easily produce very nice, high quality weight and muscle gains, it´s a very poor compound for inducing strength gains(2)(3)(4). That´s very counterintuitive, and certainly many strength athletes have experienced great results in strength as well as muscle size and fat loss from HGH. Generally, many studies have focused on HGH vs. HGH and exercise, and without the exercise LBM increases but not usually maximum voluntary strength output. It should also be noted that most athletes utilizing HGH are using it in a “cocktail” with (at least) anabolic steroids, and usually with IGF, thyroid meds, and other goodies such as an Aromatase Inhibitor.
Let´s discuss exactly why this is.
Most people who are taking the plunge into HGH use have reached a dead end with their use of anabolics, and need to push through that wall. I´m sure you´ve heard about the synergistic combination of using HGH along with Anabolic Steroids, IGF, insulin and T3 (* usually synthroid, a thyroid medication). The reason is that when these hormones are used correctly together, they´ll produce a large amount of synergy, the insulin is able to shuttle nutrients into your muscle, the thyroid hormone increases your fat-burning capability, the IGF will cause muscle growth as well as helping to grow new cartilage (thus preventing injury), and the anabolic steroids like testosterone, specifically (in addition to being anabolic) can increase IGF-1, in muscle tissue(11), and maybe even increase your body´s ability to use it. Also, usually, an increased amount of IGF usually tells your body to stop producing HGH, but testosterone actually blunts this part of the Negative FeedBack Loop (12)! And the addition of an Aromatase Inhibitor will also stop conversion of testosterone into estrogen; estrogen reduces IGF levels.(13)(14) Finally, the HGH does, well everything I just spent the last few pages telling you about!
Thus, IGF, Testosterone (and of course other steroids), Insulin, thyroid meds, and HGH will all combine to produce a pretty damned effective fat-burning and muscle building cycle! You know what else? HGH is virtually undetectable on any sort of currently used drug-screening tests. HGH, Insulin, Thyroid meds, and IGF may also be used pretty safely by those who may be subject to drug screening tests, or as a non-HPTA suppressive “bridge” between cycles.
Finally, I´ll tell you how I´d take HGH, personally. There was a study done on continuous HGH use vs. every other day injections (ED vs. EOD for the sake of brevity), with a equal total weekly dose. Although it´s counterintuitive, every other day injections produced better total growth in the kids in this (2 and 4 year long) study. Take a look at these graphs:
Growth velocity of children treated with alternate day HGH (the darker bars) or with a daily HGH regimen before, during, and 2 yr after stopping therapy. Values are the mean ± SD. *, P < 0.05; **, P < 0.01.(10) Here´s another:-see charts below Pretreatment and cumulative 4-yr growth velocity of children treated with alternate day HGH ( the darker bars) or with a daily HGH regimen. Values are the mean ± SD. *, P < 0.00 (10)
Shooting HGH every other day more accurately replicates the pulsile frequency of HGH, and thus gave better results for growth (height) deficient children, HGH pulsatility is necessary for proper function of the HGH receptor.(10) Dosing in the EOD nature reduces incidence of any sort of withdrawal problems associated with normal HGH use, including regression or retardation of growth after cessation of therapy.
Therefore, I feel very comfortable speculating that the use of HGH in this manner, which more closely simulates the natural secretion pattern of it, allows the HGH receptors and the rest of the body to more efficiently recover from it, and this will result in much more muscle growth over time (although height was examined in the previous study). My recommendations therefore are 2 shots per day of .028iu/kg of bodyweight, taken every other day, for a minimum of 3months, and preferably for 2-3x that long, and preferably with the other synergistic compounds we´ve just taken a look at.
Buying HGH (Somatotropin)
You should be paying between $1.75-2.75 per IU of HGH, and since you are going to (necessarily) be buying it in bulk, you should be paying closer to the lower end of that.
Effects of Human Growth Hormone on Body Composition in Elderly Men
Daniel Rudman, Axel G. Feller, Lester Cohn, Kaup R. Shetty, Inge W. Rudman, Michael W. Draper
Departments of Medicine, Medical College of Wisconsin, Milwaukee, Wisc, and Chicago Medical School, North Chicago, Ill.; Medical Services, Veterans Affairs Medical Centers, Milwaukee, Wisc, and North Chicago, Ill; Eli Lilly Research Laboratories, Indianapolis, Ind., USA
Address of Corresponding Author
Horm Res 1991;36 (Suppl. 1):73-81 (DOI: 10.1159/000182193)
Body composition changes progressively in mid and late adulthood. Lean body mass in men over 50 years old contracts at an average rate of-0.6% per year. Body weight tends to remain stable because of a reciprocal expansion of adipose mass. The shrinkage of the lean body mass reflects the atrophy of skeletal muscles, skin and visceral organs. Because growth hormone causes expansion of the lean body mass and contraction of the adipose mass, and because growth hormone secretion tends to diminish in late adulthood, it has been postulated that geriatric hyposomatotropism is a contributory cause to the body composition changes described above. The authors have tested this hypothesis by recruiting 45 independent men over 61 years old with plasma somatomedin C level below 0.35 U/ml, indicating little or no detectable growth hormone secretion. The 21-month protocol was as follows: baseline period 0–6 months, experimental period 6–18 months and post-experimental period 18–21 months. During the experimental period, 26 men (group I) received approximately 0.03 mg/kg of biosynthetic human growth hormone (hGH) subcutaneously 3 times a week, while 19 men (group II) received no treatment. Plasma somatomedin C was measured monthly. The following outcome variables were measured at 0,6, 12 and 18 months: lean body mass, adipose mass, skin thickness (dermis plus epidermis), sizes of the liver, spleen and kidneys, the cross sectional areas often muscle groups, and bone density at 9 skeletal sites. Lean body mass and adipose mass were also measured at 21 months. In group I, hGH treatment raised the plasma somatomedin C level and maintained it in the range 0.5–1.5 U/ml. Significant changes occurred in the following outcome variables, expressed as percent change at 18 months over baseline: lean body mass +6%, adipose mass -15%, skin thickness +4%, liver volume +8%, spleen volume + 23%, sum of ten muscle areas +11 %. Three months after hGH treatment stopped, about one half of the hGH-induced increment in lean body mass had disappeared and about one third of the hGH-induced decrement in adipose mass had reappeared. During hGH treatment, 9 subjects developed carpal tunnel syndrome and 4 subjects developed gynecomastia. The adverse side effects disappeared spontaneously within 3 months after cessation of hormone treatment. In group II, the somatomedin C level remained below 0.35 U/ml. At the 18-month time point, there was a significant decline in lean body mass to 96% of initial baseline and in skin thickness to 94% of initial baseline. These observations are consistent with the hypothesis that diminished growth hormone secretion in the later years of adulthood is a contributory cause to the body composition changes which occur with advancing age.
The following part of this article is an excerpt written by Bill Roberts:
There are primarily two theories as to how GH exerts its growth promoting effects. The first theory is called the Dual Effector theory. The second theory is called the Somatomedin (“mediator of growth”) Hypothesis. Both theories are fairly strait forward. Let?s start with the Dual Effector theory.
The Dual Effector theory states that GH itself has anabolic effects directly on body tissues. This theory has been supported by studies looking at the effects of injecting GH directly into growth plates. Genetically altered strains of mice have also help to support this theory. When comparing mice that genetically over express GH and mice that over express insulin-like growth factor-1 (IGF-1), GH mice are larger. Those who support the dual effector theory site this evidence. Interestingly, when IGF-1 antiserum (it destroys IGF-1) is administered concomitantly with GH, all of the anabolic effects of GH are abolished. Clearly IGF-1 has got to be involved somewhere between the pituitary and the target tissue (i.e. muscle). The Somatomedin hypothesis clears things up somewhat.
The Somatomedin hypothesis states that GH exerts its growth promoting effects through IGF-1. More specifically, GH is first released from the pituitary and then travels to the liver and other peripheral tissues where it causes the synthesis and release of IGFs. 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. Many studies have been performed showing that animals that are GH deficient, systemic IGF-1 infusions lead to normal growth. Admittedly, the effects are similar to those observed after GH administration. In fact, additional studies have shown IGF-1 to be greatly inferior as an endocrine growth factor requiring almost 50 times the amount to exert that same effects of GH. 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) have consistently validated the somatomedin hypothesis (Rank, 1995; Savage, 1993). These results indicate that although IGF-1 might be the mediator of GH effects, it’s not as simple as just getting the liver to release IGF-1.
So the main difference between these two theories is that the Dual effector theory states that GH doesn?t necessarily need IGF-1 to work, the Somatomedin hypothesis insists it does. In reality both theories are correct. It?s just that the Somatomedin hypothesis focuses on “circulating” IGF-1, the Dual Effector theory recognizes that although IGF-1 is still the active hormone, it doesn’t have to come from the blood (liver), it can be produced on location by the very cells that use it.
In summary, by combining the Dual Effector theory and the Somatomedin hypothesis there are three main mechanisms by which GH makes things grow. First, the effects of GH on 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.
Second, 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.
Third, GH may influence the activity of IGF-1 on an autocrine/paracrine level. Autocrine means that a hormone has an effect on the cell that produced it, paracrine means to have an effect on the “cell(s)” next to it as well. This is a completely localized effect, not dependent on the blood stream to carry things where you want them. Muscle growth from weight training is the result of IGF-1 being produced by the muscle cells themselves, not the liver. In fact, IGF-1 form the liver is genetically different from IGF-1 produced in your muscles. This information should explain why using IGF-1 systemically (from the blood stream) has been a hit and miss proposition.
In order to sufficiently address the role of GH and IGF-1 in muscle growth, we need to explore the mechanism of not only IGF-1?s autocrine/paracrine actions, but also the mechanisms of muscle growth itself.
The ability of muscle tissue to constantly regenerate in response to activity makes it unique. Its 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. Under the influence of IGF-1 these cells divide (proliferate) and genetically change (differentiation) 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 proteins come from. The larger the muscle, the more nuclei you need to maintain protein synthesis. There is a “nuclear to volume” ratio that cannot be overridden. Whenever a muscle grows in response to mechanical overload (i.e. weight training) there is a positive correlation between the increase in the number of myonuclei and the increase in muscle cell’s cross sectional area (CSA). When satellite cells are prohibited from donating new nuclei, overloaded muscle will not grow. So you see, one important key to exercise induced muscle growth is the activation of satellite cells by growth factors such as IGF-1.
Few people realize that 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. I’m not really sure why someone would choose to inject oil instead of IGF-1. Oil gives you lumps and causes your peers to make jokes about you behind your back. IGF-1 just makes the muscle grow and leaves people wondering how you brought up those lagging rear delts.
Scientists are now figuring out 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 calcineurin signaling pathway, and subsequent muscle fiber hypertrophy. I am by no means a geneticist so I hesitated even bringing this research up. To avoid confusion I will enlist the help of the people doing the research. 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. Simple huh?
Anybody really interested in how muscles grow is going to have to brush up on their genetics (including myself). Until then please don’t send me a barrage of questions about GATA-2 or NF-Atc isoforms. These aren’t things we know how to directly manipulate with supplements yet.
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