Far too detailed for me to explain here.

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.

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.

I'm sure you understand this more than me, but if IGF-1 increases protein synthesis and the uptake of amino acids - as does steroids through a different mechanism, a combination of the two would surely magnify gains no matter what the drug used. But the presence of sufficient GH would be necessary. Now, what about the negatives the doc discusses?? Is it a waste? E2 says that IGF-1 is so unstable as to be nearly impossible to work with.

Thompson SH, Boxhorn LK, Kong WY, Allen RE.

"Trenbolone alters the responsiveness of skeletal muscle satellite cells to fibroblast growth factor and insulin-like growth factor I."
Endocrinology. 1989 May;124(5):2110-7.