Anabolism is really about 3 things. One (1) increasing protein synthesis to max out the existing machinery. But once that occurs there is no more anabolism. Existing machinery can probably has the capacity to increase protein synthesis by 15% to 20% and after that you need more machinery. By machinery I mean more DNA, more DNA reads, more taking those protein manufacturing plans to more ribosomes where the proteins can actually be made. All of this talk about how to increase protein synthesis is just boring to me because there are a lot of ways to do it. ...I almost feel that if you are enhanced you're going to increase protein synthesis one way or the other. It's kinda like throwing spaghetti at your open mouth, eventually you'll fill up. Maybe the twirling the fork to the left is a better way... let all the bodybuilding gurus argue over how best to get the spaghetti in the open mouth. For my part I say just open your damn mouth.
The more interesting aspect is how to go about increasing the machinery which will do what machinery does -> protein synthesis. If you have maxed out the existing machinery's capacity for protein synthesis you need to move in more machinery and that's where GH and IGF-1 Mod GRF (1-29)/GHRPs and to some extent testosterone come into play.
IGF-1 plays a role, performs a function. It is a differentiation. By this I mean it moves the new machinery into place (2). BUT there first has to be new machinery made. That's where proliferation comes into play (3). It is the special IGF-1 called IGF-1EC (or Mechano Growth Factor) which is proliferative. Mod GRF (1-29)/GHRP and pulsed GH can increase MGF (MGF is made and used in muscle cells... it is not made in the liver and sent out systemically in blood). GH elevations can also increase MGF BUT GH elevations also increase IGF-1 which can interfere with MGF.
It is more difficult to keep proliferation going then it is to bring about differentiation because differentiation always cuts short proliferation as soon as it is introduced.
So building more DNA and donating it to muscle cells is hugely important. Once that new DNA is in place you can keep doing what you do to keep protein synthesis going in all the old and now new DNA machinery.
Studies & observations have been done which looked at different people all natural as they enter weightlifting for the first time. All grow as protein synthesis increases. But as time goes on some continue to grow really well, others grow but not as much and some just don't grow much anymore. The DIFFERENCE between people is to what extent if any do they increase their protein synthesis machinery. Some may do it easily. By that MGF-proliferation occurs post workout and over the next 48 hours and then IGF-1 takes those proliferated nuclei and fuses them into muscle cells and then IGF-1, GH pulses and natural testosterone, even insulin contributes to increasing the protein synthesis which comes from the new machinery.
When you run into those people who honestly go to the gym, work and eat just as hard as everyone else, get stronger but don't grow much it is because genetically they aren't triggering this proliferative->differentiation process... this interplay between IGF-1EC and IGF-1.
Now if I can step away from this for a 2nd and move into the difference between systemic IGF-1 and local IGF-1 or muscle IGF-1, I will be able to say muscle IGF-1 IS IMPORTANT!!!!!!!!! In the same breadth I can say that what is made in the liver and circulated (you know the stuff you can measure on a blood test) is not important for muscle growth.
Some tissue makes its own IGF-1 and muscle happens to be one of those tissues. When you inject a lot of IGF-1 or have a lot of GH elevations you flood the body with IGF-1. That blood IGF-1 gets taken up only in tissue that isn't making much of it's own. You see IF tissue makes it's own it does something kinda cool. It makes the receptor and the IGF-1 inside the cell and binds the two before releasing this omplex to the surface. Only when this complex pops out of the cell onto the membrane does it activate IGF-1 signalling. If you need a mental picture, then make IGF-1 a golf ball and the IGF-1 receptor the tee. Local muscle IGF-1 (ball) gets placed on the receptor (tee) inside the cell and then moved to the membrane (tee box).
Now that means that IGF-1 made in the liver or injected floating by from the blood will not get a chance to bind to receptors since most that are expressed are preoccupied. There are very few open tees.
So where does that blood IGF-1 get taken up? Answer, where there are open tees or receptors. That tissue could be the gastrointestinal tract. Severe injury as well will have open receptors. Other tissue as well... but not muscle tissue.
Now the interesting thing is elevated GH does increase local IGFs as well but to some extent the systemic levels of IGF-1 will feedback on the neurons that inform the hypothalamus and this will increase somatostatin's influence which will inhibit a GH pulse. There may be a down regulation in intracllular signalling as well. I can say there is some unknown in this area. It is costly for an experiment to set up the procedures to measure the making and activity of local IGFs.
Now local IGF-1 IS important in another respect. It binds to it's receptor which complexes with the GH receptor and stabilizes the GH receptor. This means that GH binding to the GH receptor will last longer. This will result in an increase STAT5b activity within the cell. STAT5b is the relay that goes to the nucleus and triggers GH-induced DNA-RNA-protein synthesis of certain factors such as the IGF family (IGF-1 & IGF-1EC (MGF). So one pulse of GH will increase local IGF-1 which will create stability for the GH-GH receptor complex which will take place for the next pulse. This is one reason pulses spaced at 3-3.20 hours apart appear optimal.