Excerpt for an excelent article on Growth Hormone

[hailtotheking]

This is taken from an article by John Berardi called "The Fountain of GH: Does it Work?"

GH — The Hormone
Growth hormone (GH) is a 191-amino acid protein or peptide that's naturally released from the pituitary gland. GH, much like Testosterone, is released in a pulsatile or episodic manner. The GH pulse occurs every 2-3 hours so each and every day we get about 8-12 big doses of all-natural growth hormone (Hartman et al 1991). The sum of these GH peaks amounts to about 0.5 mg of GH produced per day. The following is an example of what normal 24 hr GH production might look like, with the highest peaks occurring during the first few hours of sleep:


According to the research review published in a new textbook entitled "Growth Hormone in Adults," the release of GH from the pituitary is governed by a balancing act between 2 hormones; GHRH (growth hormone releasing hormone) and somatostatin. GHRH is responsible for stimulating both the synthesis and the release of GH from the pituitary. Essentially, GHRH initiates the strength of the GH pulse.
GHRH's arch rival, somatostatin, counters these effects, however, by inhibiting GH release. Therefore, somatostatin prevents the GH pulse. In the end, GH release occurs when GHRH is at its peak in stimulating the pituitary, while somatostatin is at its low in inhibiting the pituitary. The result of this high GHRH and low somatostatin period is a big spike in blood levels of GH (Juul, 2000).
The following is a chart adapted from Basic and Clinical Endocrinology, 5th Edition depicting other factors influencing the GH secretion spike:
Factors Increasing GH Secretion Factors Decreasing GH Secretion
Physiological: Physiological:
Sleep Hyperglycemia
Fasting Elevated Blood Free Fatty Acids
Exercise Obesity
High Amino Acids
in the Blood Hyper or Hypothyroidism
Low Blood Sugar
Pharmacologic: Pharmacologic:
Any hypoglycemic agent GH itself
Estrogens Somatostatin
Alpha-agonists Alpha antagonists (yohimbine)
Beta antagonists Beta agonists (ephedrine, clenbuterol)
Serotonin Serotonin antagonists
Dopamine Dopamine antagonists
GABA
Once the GH pulse occurs, blood GH is free to affect target tissues. Some of the well-documented actions of GH are increases in longitudinal bone growth (longer bones), increased bone mineralization (thicker, stronger bones), anabolism (protein building), lipolysis (fat loss), and anti-diuretic actions (Bengtsson, 1999). GH treatment is common in congenital syndromes of GH deficiency and in cases of hypothalamic or pituitary damage.
In addition, it's been recognized that around the age of 30, there's a progressive decline in GH secretion from the pituitary, so much so that by the age of 60, GH production can drop as much as 60%! This means that an aging pituitary that once produced 0.5 mg of GH per day would now produce only 0.2 mg per day, and this is definitely physiologically relevant. In fact, these production levels are often equivalent to those of GH deficient young adults. This age-related GH decline has been termed somatopause by some researchers and treatment requires GH replacement therapy.

GH Deficiencies
GH deficiencies in different populations can occur as a result of impaired GHRH activity or increased somatostatin activity, impaired GH production and release within the pituitary, and/or impaired GH interactions with GH receptors on target tissues (Bengtsson, 1999). Basically GH either isn't produced or the GH is knockin' but it can't come in. Regardless of the mechanism behind GH deficiencies, these conditions can lead to a whole host of physiological abnormalities.
In children, GH deficiency leads to a reduced growth rate. This can occur due to the lack of GH specific effects on bone and connective tissue growth. In addition, skeletal muscle growth can be retarded due to other metabolic abnormalities associated with GH deficiency (decreased protein anabolism).
In adults, there are a number of abnormalities associated with GH deficiency. First, GH deficient adults tend to suffer from a host of psychological symptoms. These symptoms include reduced energy levels, reduced vitality, increased anxiety, reduced emotional reaction, depression, hampered learning capacity, and social isolation (Bjorck, 1989).
Secondly, GH-deficient adults suffer from negative changes in body composition such as increased fat mass, especially in the abdominal area (called android fat distribution), decreased lean body mass and muscle volume, and reduced bone mineral content (Binnerts 1992, Bengtsson 1993, Rosen 993). As a result of these negative changes in body composition, decreased muscular strength, poor exercise capacity, and poor power output are a result (Cuneo 1990, 1991).
Finally, GH deficiency can lead to other symptoms such as dehydration, reduced heart size, reduced cardiac performance (measured by cardiac contractility and output), hypertension, and hypothyroidism (due to low T4 to T3 conversion) (Henneman 1960, Shahi 1992, Jogensen 1989).
The bottom line is that if you can't get GH to do its job in the body, your psychological state, body composition, muscular performance, and cardiac performance will suffer. So you'd better get some GH.

Hey Doc, How's My GH?
So how do you know if you need GH treatment? That's a good question that scientists are still trying to answer. And you can bet that if they're having a hard time with this question, most physicians are quite a bit behind them. Since the symptoms of GH deficiency in adulthood (increased adiposity, decreased muscle mass, reduced strength and exercise capacity, and psychological disturbances) are non-specific, a deficency based on clinical symptoms is difficult to diagnose. Therefore, biochemical markers must be used.
Random sampling of plasma GH isn't a sufficient measure due to the unpredictable pulsatile nature of GH secretion shown in the graph above. If you pull a sample at the peak of a GH burst, it looks like you're fine, but if you pull one at the "trough"; it looks like you need some GH. Normal fasted levels of GH are less than 5 ng/ml, but again, the utility of random sampling is limited. By taking a 24-hour integrated measure, you could get a good approximation of total GH secretion, but who wants to sit in the doctor's office for 24 hours and have 24 blood samples taken; one every hour? Not me!
Therefore, the best clinical test for GH secretory deficiency is an ITT or insulin tolerance test. With this test, a single dose of insulin is administered to promote hypoglycemia. If you check your chart above, you'll notice that hypoglycemia is a good GH secretory stimulant. So, as insulin goes up and blood glucose goes down, GH secretion should go up. Since this test only measures GH secretion and not GH action at the receptor level, other tests are required to determine GH deficiency.
Serum measures of IGF-1 and IGFBP-3 are two markers of GH activity but their utility has been questioned (more on these later). Since daily IGF-1 levels tend to be stable, in the clinical setting, low IGF-1 levels can indicate the need for further assessment of GH secretion and function. Normal IGF-1 levels are 90-318 micrograms/l while IGFBP-3 levels are 2.0-4.9 milligrams/l.

Effects of GH Replacement
Since GH deficiency leads to the aforementioned frightening list of psychological and physiological abnormalities, the treatment of GH deficiency has received much attention within the medical community.
In clinical trials, most of which were referenced above in the "deficiency" section, GH replacement has been shown to remedy most of the physiological abnormalities. The major benefits of GH therapy include positive protein balance (synthesis exceeds breakdown), increased lean body mass, decreased fat mass, increased insulin sensitivity, normalized body water, increased bone remodeling, and increased T4 to T3 conversion.
What about side effects? In GH deficient patients, replacement therapy is usually associated with minimal side effects. The most common side effects typically occur with the onset of therapy but often tend to normalize within a few months' time. These negative side effects include include fluid retention, carpal tunnel syndrome, myalgia (muscle pain), and arthralgia (joint pain). In addition, fasted and post-prandial (post-meal) blood glucose levels tend to be higher in GH replacement as a result of the mild insulin insensitivity that can occur with doses in excess of the exact requirement. Finally, it's been suggested, but not verified, that GH replacement may lead to a risk of malignancy and some cancers.
Although there are a few risks with GH replacement, the risk to benefit ratio of GH therapy in grossly deficient humans remains positive. Since GH can be relatively safe in replacement situations, as well as the fact that GH treatment can greatly impact body composition, researchers and clinicians have begun to explore the use of GH in treating the negative physiological conditions caused by HIV or age-related muscle wasting, obesity, severe physiological stressors (surgery or burn injuries), nutrient restriction, glucocorticoid therapy, and impaired immunity. Unfortunately, the data are mixed in regard to GH therapy in these populations with some studies showing positive results in muscle mass and fat loss and others showing nothing but side effects.
One reason for this may be the fact that in some studies, GH treatment has been given alone while in others, GH treatment was given with several other hormones that may have acted synergistically with the GH to promote the positive changes. One thing is clear though; there is no clarity! At the doses given in research studies, there is no clear consensus on whether GH therapy is warranted in any population other than those with GH deficiency. More research is needed to make this determination.

[hailtotheking]

How GH Works — The GH/IGF-1 AXIS
Due to the rise in recombinant GH availability, the research has been abundant and a clearer picture is emerging of GH action. But make no mistake, the picture isn't all that clear. It may be more like one of those computer-generated 3D pictures that you have to look at in just the right way for just the right amount of time to make any sense of it at all. And no one has yet to look long enough at this particular picture.
With all of this GH floating around, the black market supply of GH has also been on the rise. So after we talk GH action, let's talk bodybuilding. If GH can potentially get bodybuilders big and ripped, then to some, it's a drug worth exploring. So for you die-hard muscle heads, here's a little GH primer with special focus on the pursuit of lean mass.
Circulating GH is thought to act through two distinct but interrelated mechanisms. The first is direct. GH can act directly on many cells in the body via the GH receptor. Once released into the blood from the pituitary, GH either circulates as free GH or circulates bound to GHBP for transport (GH Binding Protein). Free GH is available to interact with cellular receptors to create a response.
Once free GH has interacted with the cellular receptors, it's thought that more GHBPs are formed. With this increased GHBP, some researchers believe that more GH is rendered temporarily unavailable. But at the same time, it stays in the system for a longer amount of time. So although GHBP-bound GH has a much longer half-life, it cannot interact with cellular receptors while bound.
Unfortunately, there's no clear consensus as to whether it's more important to cellular GH action to prolong the half-life of GH (to allow for higher levels to circulate for longer), or to decrease GHBP to allow for higher levels of free GH. And this debate holds true for not only GH, but for other hormones like Testosterone as well. Although the researchers tend to contradict each other and sometimes even themselves on this point, the bottom line is that the effectiveness of GH (and other hormones) is tied up in this balance between bound and unbound GH and the presence of binding proteins.
Binding proteins aside, once free GH does reach the cells, its direct actions include the promotion of lipolytic and hyperglycemic effects. GH can decrease glucose utilization in favor of fat release and oxidation (lipolysis). Unfortunately, because of this shift from carb to fat use, GH also increases insulin resistance. Hyperglycemia is a result of this insulin insensitivity. So although GH itself can make you lean due to lipolysis, this might come at the expense of insulin resistance and might ultimately lead to a diabetic state. As a result, you'll be a lean diabetic rather than a chubby normal guy. I guess it's a trade-off.
The second mechanism by which GH exerts its effects is indirectly through IGF-1. In the liver, circulating GH is converted into IGF-1 and 2 which can travel through the blood to promote their effects. IGF is also bound to one of 6 plasma proteins (IGFBP's 1-6). About 1-5% of IGF-1 is free while 95-99% is bound. Again, this balance is important for hormone action. This systemic IGF is also free to interact with cellular receptors.
In addition to the systemic effects of liver IGF-1, IGF can act locally. Let me explain. GH binding to cells can lead to what is called peripheral conversion of IGF-1. At this specific location (skeletal muscle for example), IGF-1 acts in an autocrine or paracrine fashion to promote its effects. This means that unlike GH, which has endocrine function (it is produced in the pituitary and travels elsewhere to do its work), IGF-1 can both be produced in, and promote changes in, the same tissue or those immediately adjacent to it.
Perhaps the most relevant effect of IGF-1 to this discussion is the ability of IGF-1 to increase protein synthesis by increasing cellular mRNA formation (mRNA makes protein) as well as increasing uptake of amino acids. This effect on protein synthesis can lead to increased lean mass. The research indicates that this effect is dependent on GH presence as well. So IGF-1 alone does not promote such effects. Nor does GH. It appears the combination of the two most consistently lead to increased protein synthesis.
In addition, IGF-1 can also counteract the hyperglycemic effects of GH via insulin-like actions on glucose uptake. Since IGF-1 is typically elevated to a small extent with GH elevations, IGF action is not sufficient to neutralize the hyperglycemic effects of GH, but perhaps it minimizes extreme insulin insensitivity.
The bottom line is that GH and IGF-1 seem to be necessary bedmates. Although each may act most strongly in different tissue types, they are thought to work together to promote anabolism and stimulate lipolysis (Ney 1999, Yarasheski 1994). But all this synergy comes at a price. Both hormones negatively feed back on the pituitary to slow GH production. And this impacts normal GH secretion as well as GH treatment.
When plasma GH levels and IGF-1 levels are elevated with GH treatment, this elevation is non-physiologic. What this means is that after a GH injection, GH levels are elevated for some time and then come crashing down to normal, often being suppressed for hours thereafter. So the pattern seen in the graph above is not the one seen when using exogenous GH. This is probably due to the fact that both GH and IGF-1 are negative regulators of GH release so an increase in either (from a GH injection) reduces the secretion of GH.

[cheef]

good post

[MeshMan]

Nice

Few things above my head (lypolysis, hyperglycemic, insulin resistance etc.) but prompting me to go Wikipedia them and learn, thanks dude!

[Aren_Tyr]

Terrific post. And also illustrates that one shouldn't go messing with exogenous supplementation of these hormones; the complexity of their working is still not fully understand.

And as usual, as soon as you start unnaturally elevating a particular hormone in the blood, you effectively start to shut down the body's natural production of that hormone.

So the emphasis moves back to finding ways to naturally maximise GH/IGF-1 levels to their optimum levels, and slow their decline with age as much as possible.

Currently it appears that regular resistance training, excellent diet, good sleep patterns, and low stress is the best method for achieving this.

[kp1512]

Quote

Effects of GH Replacement
Since GH deficiency leads to the aforementioned frightening list of psychological and physiological abnormalities, the treatment of GH deficiency has received much attention within the medical community.
In clinical trials, most of which were referenced above in the "deficiency" section, GH replacement has been shown to remedy most of the physiological abnormalities. The major benefits of GH therapy include positive protein balance (synthesis exceeds breakdown), increased lean body mass, decreased fat mass, increased insulin sensitivity, normalized body water, increased bone remodeling, and increased T4 to T3 conversion.
What about side effects? In GH deficient patients, replacement therapy is usually associated with minimal side effects. The most common side effects typically occur with the onset of therapy but often tend to normalize within a few months' time. These negative side effects include include fluid retention, carpal tunnel syndrome, myalgia (muscle pain), and arthralgia (joint pain). In addition, fasted and post-prandial (post-meal) blood glucose levels tend to be higher in GH replacement as a result of the mild insulin insensitivity that can occur with doses in excess of the exact requirement. Finally, it's been suggested, but not verified, that GH replacement may lead to a risk of malignancy and some cancers.
Although there are a few risks with GH replacement, the risk to benefit ratio of GH therapy in grossly deficient humans remains positive. Since GH can be relatively safe in replacement situations, as well as the fact that GH treatment can greatly impact body composition, researchers and clinicians have begun to explore the use of GH in treating the negative physiological conditions caused by HIV or age-related muscle wasting, obesity, severe physiological stressors (surgery or burn injuries), nutrient restriction, glucocorticoid therapy, and impaired immunity. Unfortunately, the data are mixed in regard to GH therapy in these populations with some studies showing positive results in muscle mass and fat loss and others showing nothing but side effects.
One reason for this may be the fact that in some studies, GH treatment has been given alone while in others, GH treatment was given with several other hormones that may have acted synergistically with the GH to promote the positive changes. One thing is clear though; there is no clarity! At the doses given in research studies, there is no clear consensus on whether GH therapy is warranted in any population other than those with GH deficiency. More research is needed to make this determination.

I thought this was interesting.

The Aids\HIV arena has shown some excellent data on numerous trials on preserving muscle tissue, and outside of hGH abnormalities is an area which probably utilises GH the most.

Personally, taking Ex HGH is just a recipie for disaster if youd ont know what you are doing....and as we can see this is another reason why we see the state of BB today as it is......

KP

[hailtotheking]

So when examining the GH/IGF-1 axis, a few things should be considered. With strong feedback mechanisms in place, it's difficult to maintain consistently high levels of GH without constant exogenous dosing. And that's a hassle. In addition, just like with insulin, there may be something known as GH insensitivity (Grinspoon 1998). It appears that with chronically high levels of GH, liver and peripheral conversions of GH to IGF-1 are decreased. So even with the constant use of exogenous GH, the body may simply try to regulate itself and the actions of GH by preventing the availability of what is thought to be GH's partner, IGF-1.
It seems like a no-win situation. And perhaps this is best. The body has feedback mechanisms for a reason� protection. If GH action isn't kept in check, the medical condition known as acromegaly can result. Acromegaly is characterized by abnormal skeletal growth characterized by enlarged jaw and hands. Individuals suffering from this have abnormally high levels of GH, IGF-1, and IGFBPs. It's apparent, then, that the feedback mechanisms of these individuals aren't working all that well.
Often times, GH users smugly tell me that acromegaly is BS because they've been using GH for X amount of time and they didn't get it. Well guys, guess what? Normal individuals probably won't get it because of the feedback mechanisms described above. You know what else? You're probably not getting muscle building results either.

The Perfect Physique?
GH, Muscle Function, and Body Composition Research
Since most of the benefits of GH were originally thought to impact muscle mass, scores of rodent studies were conducted to examine the effect of GH on muscle mass and contractile ability. The findings did indicate a small increase in muscle mass but no increase in contractile strength. One study looked at rat quads (no they didn't squat) and they did get bigger (quads), but not stronger (Bigland, 1953). In addition, in other rat studies, although there were small increases in body mass, there were absolutely no increases in strength. How could this be? More muscle equals more strength, right? Well, researchers concluded that the increase in quad mass was not contractile protein. The mass could have been fluid or connective tissue.
Since animals did benefit from increased muscle mass, the next step was to take these findings to humans. In cases of GH deficiency, small increases were found in muscle volume (~6-8%) and lean body mass (~11%). Exercise capacity was elevated in such patients (~12%), but strength was either not changed or mildly increased by about 8% (Jorgensen 1989, Salomon 1989). As stated earlier, most of the observed benefits of GH have been seen in GH deficient animals and humans.
Also, as mentioned earlier, there's certainly not much to get excited about in other populations. When GH is administered alone, very few studies have shown any increase in size or strength. In two recent HIV studies, patients given huge doses of up to 27 IU per day (9 milligrams) had no gains in muscle mass. But remember, according to what I said earlier, IGF-1 was the protein anabolic agent. And GH has its biggest effect on lipolysis. And the combination of the two may lead to the greatest results.
So in examining the research, it's been speculated that the levels of IGF-1 adminstered weren't great enough (in conjunction with GH) to make an impact, or that the individuals became GH resistant. Also, since IGF-1 would lower GH secretion, it doesn't make much sense to give it alone. Remember, GH and IGF-1 often work together to change body composition. Newer studies have shown that when adding IGF-1 to the mix, it appears that there's a definite increase in protein synthesis and muscle mass as well as some increase in strength.
So perhaps GH alone is useless at increasing muscle mass while a combination of GH and IGF-1 may be effective if protein anabolism and increased contractile protein is the goal (Kupfer 1993, Snyder 1988). But even the increases seen in these studies were moderate and a cost/benefit analysis is warranted since this combination might also lead to severe side effects.
So what about GH and fat mass? Most studies have shown modest decreases in body fat and skinfold measures with GH treatment (Jorgensen 1989, Salomon F, Tagliaferri 1998). Decreases in fat mass of about 16% and decreases in thigh adipose mass of about 7% have been reported. But remember, a 16% fat decrease doesn't mean they went from 20% to 4% body fat. It more likely means that a 200 lb person with 20% bodyfat or 40 lbs of fat would have their fat mass decreased to about 35.5 lbs. This would put them at about 193.5 lbs and 18% fat.
In another study, obese women on GH lost 2 more lbs than placebo group in a one-month period. So although it does appear that GH can decrease fat mass in clinical populations, when looking at the actual fat loss numbers, it appears that the good old ECA stack or [competitor product] would be more effective than GH.

[hailtotheking]

There was more to the article concering the actual use of GH in relation to other anabolic substances, but that is a bit 'grey area'.

[kp1512]

I think it just states a few more obvious known elements within the bodybuidling arena that

- GH is just an expensive fat loss hormone if taken alone
- too much GH does more damage then taking the right amount
- Ex GH needs to be taken with an androgen to get the best results

KP