After a discussion over at myprotein.co.uk, I was posed the question as to what I think actually causes muscular hypertrophy, and it suddenly occured to me that from a cellular and signalling perspective the initiator has to be substrate turnover. ( By substrate turnover I mean the total amount of molecules burned for energy, and in particular, the amount of anaerobic energy used. )
There is alot of evidence to support this. There are those studies showing much higher increases in mass and strength gains when rest between sets is extended, such as in this one.
There are also all those studies showing that a greater of sets are more anabolic compared to a smaller number. I.E. that volume matters hugely. Obviously, it takes more substrate turnover to do 4 sets than it does to do 2 sets.
Not to mention we have the famous 30FAIL > 90 FAIL study. The investigator's explained thier findings with the suggestions that the size principle was behind the greater muscle protein synthesis.
While I am a firm believer in the importance of the size principle, I think it doesnt tell the story of WHY the 30FAIL group got more muscle protein synthesis. The answer I'm almost certain was becuase of a higher substrate turnover allowed in the smaller motor unit muscle fibres.
Lastly, there is the evidence that mTOR is sensitive to the redox reaction.
UPDATE - having given more thought to it, theres a chance that the initiator could be also be the degree of PCr / glycogen exhaustion. In most situations the degree of substrate usage and PCr exhaustion will be closely related, except for sets of reps that are not taken sufficiently close to failure. In reality, it is probably a combination of the 2 effects as this explains the gains that happen when working with very high % or 1RM (90% and over )